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1
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Zheng Q, Bao P, Wu X, Zhang X, Huang C, Wang T, Ma C, Zhang M, Chu M, Guo X, Liang C, Pan H, Yan P. Integration of bulk and single-cell RNA sequencing reveals dynamic changes in epidermal cells. Int J Biol Macromol 2025; 309:142601. [PMID: 40158578 DOI: 10.1016/j.ijbiomac.2025.142601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 03/12/2025] [Accepted: 03/26/2025] [Indexed: 04/02/2025]
Abstract
The epidermis and its appendages serve as key systems in stem cell biology. However, despite extensive research, the dynamic changes in these structures and the regulatory mechanisms governing cell behavior during the hair follicle cycle remain incompletely understood. In this study, we employed bulk and single-cell RNA sequencing to investigate the molecular regulation of yak epidermal cell populations across the anagen, catagen, and telogen phases. Through bulk transcriptomics screening, the hub genes potentially involved in the hair follicle cycle of yaks were identified. Single-cell RNA sequencing further revealed the temporal and spatial dynamics of 14 different cell populations in the hair follicle cycle, and reconstructed the trajectory of epidermal cell differentiation. We also found a large overlap of gene modules in the hair follicle microenvironment. Differential gene enrichment analysis of different branches further revealed that the function of hair follicle stem cells is closely related to their spatial location in tissues and their ability to adhere to the basement membrane. Our study not only provides valuable resources for understanding the molecular pathways of the time axis and spatial axis of the hair follicle cycle but is also highly important for future yak breeding.
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Affiliation(s)
- Qingbo Zheng
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; Institute of Western Agriculture, Chinese Academy of Agricultural Sciences, Changji 831100, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China
| | - Pengjia Bao
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xiaoyun Wu
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xiaolan Zhang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Chun Huang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Tong Wang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Chaofan Ma
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Minghao Zhang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Min Chu
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xian Guo
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Chunnian Liang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Heping Pan
- Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China.
| | - Ping Yan
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; Institute of Western Agriculture, Chinese Academy of Agricultural Sciences, Changji 831100, China; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518000, China.
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2
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Makkar J, Flores J, Matich M, Duong TT, Thompson SM, Du Y, Busch I, Phan QM, Wang Q, Delevich K, Broughton-Neiswanger L, Driskell IM, Driskell RR. Deep Hair Phenomics: Implications in Endocrinology, Development, and Aging. J Invest Dermatol 2025; 145:800-811.e8. [PMID: 39236901 PMCID: PMC11873809 DOI: 10.1016/j.jid.2024.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 08/08/2024] [Accepted: 08/11/2024] [Indexed: 09/07/2024]
Abstract
Hair quality is an important indicator of health in humans and other animals. Current approaches to assess hair quality are generally nonquantitative or are low throughput owing to technical limitations of splitting hairs. We developed a deep learning-based computer vision approach for the high-throughput quantification of individual hair fibers at a high resolution. Our innovative computer vision tool can distinguish and extract overlapping fibers for quantification of multivariate features, including length, width, and color, to generate single-hair phenomes of diverse conditions across the lifespan of mice. Using our tool, we explored the effects of hormone signaling, genetic modifications, and aging on hair follicle output. Our analyses revealed hair phenotypes resultant of endocrinological, developmental, and aging-related alterations in the fur coats of mice. These results demonstrate the efficacy of our deep hair phenomics tool for characterizing factors that modulate the hair follicle and developing, to our knowledge, previously unreported diagnostic methods for detecting disease through the hair fiber. Finally, we have generated a searchable, interactive web tool for the exploration of our hair fiber data at skinregeneration.org.
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Affiliation(s)
- Jasson Makkar
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Jorge Flores
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Mason Matich
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Tommy T Duong
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Sean M Thompson
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Yiqing Du
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Isabelle Busch
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Quan M Phan
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Qing Wang
- Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Kristen Delevich
- Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA; Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Liam Broughton-Neiswanger
- Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
| | - Iwona M Driskell
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA
| | - Ryan R Driskell
- School of Molecular Biosciences, Washington State University, Pullman, Washington, USA; Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
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3
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Vasu M, Ahlawat S, Arora R, Sharma R. Deciphering the molecular drivers for cashmere/pashmina fiber production in goats: a comprehensive review. Mamm Genome 2025; 36:162-182. [PMID: 39904908 DOI: 10.1007/s00335-025-10109-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 01/29/2025] [Indexed: 02/06/2025]
Abstract
Cashmere, also known as pashmina, is derived from the secondary hair follicles of Cashmere/Changthangi goats. Renowned as the world's most luxurious natural fiber, it holds significant economic value in the textile industry. This comprehensive review enhances our understanding of the complex biological processes governing cashmere/pashmina fiber development and quality, enabling advancements in selective breeding and fiber enhancement strategies. The review specifically examines the molecular determinants influencing fiber development, with an emphasis on keratins (KRTs) and keratin-associated proteins (KRTAPs). It also explores the roles of key molecular pathways, including Wnt, Notch, BMP, NF-kappa B, VEGF, cAMP, PI3K-Akt, ECM, cell adhesion, Hedgehog, MAPK, Ras, JAK-STAT, TGF-β, mTOR, melanogenesis, FoxO, Hippo, and Rap1 signaling. Understanding these intricate molecular cascades provides valuable insights into the mechanisms orchestrating hair follicle growth, further advancing the biology of this coveted natural fiber. Expanding multi-omics approaches will enhance breeding precision and deepen our understanding of molecular pathways influencing cashmere production. Future research should address critical gaps, such as the impact of environmental factors, epigenetic modifications, and functional studies of genetic variants. Collaboration among breeders, researchers, and policymakers is essential for translating genomic advancements into practical applications. Such efforts can promote sustainable practices, conserve biodiversity, and ensure the long-term viability of high-quality cashmere production. Aligning genetic insights with conservation strategies will support the sustainable growth of the cashmere industry while preserving its economic and ecological value.
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Affiliation(s)
- Mahanthi Vasu
- ICAR-National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Sonika Ahlawat
- ICAR-National Bureau of Animal Genetic Resources, Karnal, Haryana, India.
| | - Reena Arora
- ICAR-National Bureau of Animal Genetic Resources, Karnal, Haryana, India
| | - Rekha Sharma
- ICAR-National Bureau of Animal Genetic Resources, Karnal, Haryana, India
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4
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Xiao Y, Zhang Y, Deng S, Yang X, Yao X. Immune and Non-immune Interactions in the Pathogenesis of Androgenetic Alopecia. Clin Rev Allergy Immunol 2025; 68:22. [PMID: 40024940 DOI: 10.1007/s12016-025-09034-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2025] [Indexed: 03/04/2025]
Abstract
Androgenetic alopecia (AGA), a leading cause of progressive hair loss, affects up to 50% of males aged 50 years, causing significant psychological burden. Current treatments, such as anti-androgen drugs and minoxidil, show heterogeneous effects, even with long-term application. Meanwhile, the large-scale adoption of other adjuvant therapies has been slow, partly due to insufficient mechanistic evidence. A major barrier to developing better treatment for AGA is the incomplete understanding of its pathogenesis. The predominant academic consensus is that AGA is caused by abnormal expression of androgens and their receptors in individuals with a genetic predisposition. Emerging evidence suggests the contributing role of factors such as immune responses, oxidative stress, and microbiome changes, which were not previously given due consideration. Immune-mediated inflammation and oxidative stress disrupt hair follicles' function and damage the perifollicular niche, while scalp dysbiosis influences local metabolism and destabilizes the local microenvironment. These interconnected mechanisms collectively contribute to AGA pathogenesis. These additional aspects enhance our current understanding and confound the conventional paradigm, bridging the gap in developing holistic solutions for AGA. In this review, we gather existing evidence to discuss various etiopathogenetic factors involved in AGA and their possible interconnections, aiming to lay the groundwork for the future identification of therapeutic targets and drug development. Additionally, we summarize the advantages and disadvantages of AGA research models, ranging from cells and tissues to animals, to provide a solid basis for more effective mechanistic studies.
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Affiliation(s)
- Yu Xiao
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China
| | - Yi Zhang
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China
| | - Shuting Deng
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China
| | - Xueyuan Yang
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China
| | - Xu Yao
- Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
- Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, Jiangsu, China.
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5
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Nai R, Zhang C, Xie Y, Man D, Li H, Ma L, Mi L, Zhao M, Mu Q, Gao L, Liu Z, Li J. A comparative proteomic-based study identifies essential factors involved in hair follicle growth in inner Mongolia cashmere goats. BMC Vet Res 2025; 21:118. [PMID: 40011909 PMCID: PMC11866830 DOI: 10.1186/s12917-025-04608-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 02/19/2025] [Indexed: 02/28/2025] Open
Abstract
Renowned for its invaluable undercoat, the cashmere goat is well known. The growth of cashmere fibre initiates when the relatively inactive telogen stage transitions to the anagen stage, which involves active proliferation. However, the molecular mechanisms responsible for this process are still unclear. Here, SWATH mass spectrometry (MS), a comparative proteomic analysis, was conducted to examine the proteomic alterations in Inner Mongolia cashmere goat skin samples at two different developmental stages (anagen and telogen). In total, 2414 proteins were detected, with 631 proteins showing differential regulation (503 upregulated proteins and 128 downregulated proteins). Bioinformatic analysis revealed that these proteins, which are differentially regulated, play crucial roles in the pathways associated with metabolism and fatty acids according to the GO and KEGG analyses. Furthermore, interactome analysis revealed that differentially regulated keratins have a crucial impact. The localization of KRT25, KRT71, and KRT82 using immunohistochemistry revealed that these proteins were expressed in the secondary hair follicles of cashmere goat skin. The keratin family plays an irreplaceable and important role in the process of hair follicle growth.
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Affiliation(s)
- Rile Nai
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
- College of Agriculture, Hulunbuir University, Hulunbuir, 021008, China
| | - Chongyan Zhang
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
- Inner Mongolia Key Laboratory of Sheep & Goat Genetics, Breeding and Reproduction, Hohhot, 010018, China
- Key Laboratory of Sheep & Goat Genetics and Breeding of Ministry of Agriculture, Hohhot, 010018, China
| | - Yuchun Xie
- College of Animal Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, 066004, China
| | - Duhu Man
- College of Agriculture, Hulunbuir University, Hulunbuir, 021008, China
| | - Haijun Li
- College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Lina Ma
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
- Inner Mongolia Fengxin Pharmaceutical Co., Ltd., Hohhot, 010010, China
| | - Lu Mi
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Meng Zhao
- Inner Mongolia Academy of Agriculture and Animal Husbandry Sciences, Hohhot, 010018, China
| | - Qier Mu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China
| | - Lixia Gao
- Baotou Light Industry Vocational Technical College, Baotou, 014035, China
| | - Zhihong Liu
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China.
- Inner Mongolia Key Laboratory of Sheep & Goat Genetics, Breeding and Reproduction, Hohhot, 010018, China.
- Key Laboratory of Sheep & Goat Genetics and Breeding of Ministry of Agriculture, Hohhot, 010018, China.
| | - Jinquan Li
- College of Animal Science, Inner Mongolia Agricultural University, Hohhot, 010018, China.
- Inner Mongolia Key Laboratory of Sheep & Goat Genetics, Breeding and Reproduction, Hohhot, 010018, China.
- Key Laboratory of Sheep & Goat Genetics and Breeding of Ministry of Agriculture, Hohhot, 010018, China.
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6
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Jung SW, Pi LQ, Jeon JJ, Kim YH, Lee S, Lee WS. Protective Effects of Korean Red Ginseng Against Oxidative Stress-Induced Damage in Human Hair. Ann Dermatol 2025; 37:1-11. [PMID: 39894668 PMCID: PMC11791020 DOI: 10.5021/ad.24.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Oxidative stress causes fatal damage to follicular keratinocytes (FKCs) and is a common pathophysiology of many hair disorders. OBJECTIVE This study investigated the protective effects of Red ginseng extract (RGE) and its main ginsenosides against oxidative hair damage using an in vitro organ model of human hair follicles. METHODS We examined whether RGE and its constituent ginsenosides could prevent oxidative damage induced by H₂O₂ in FKCs by suppressing apoptosis and promoting hair growth. RESULTS RGE and its main ginsenoside, G-Rb1, significantly inhibited reactive oxygen species production and apoptosis in FKCs. Furthermore, they effectively alleviated the inhibition of hair growth induced by oxidative damage and inhibited the transition of hair from the anagen to the telogen stage. The hair cycle and apoptosis were associated with the modulation of p53 and Bax/Bcl2 signaling. CONCLUSION RGE and G-Rb1 can effectively mitigate the oxidative damage caused by FKCs, thereby affecting hair growth and hair cycles.
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Affiliation(s)
- Seung-Won Jung
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Long-Quan Pi
- Department of Dermatology, Yanbian University Hospital, Yanji, China
| | - Jae Joon Jeon
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - You Hyun Kim
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Solam Lee
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Won-Soo Lee
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
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Seong KY, Kim MJ, Lee H, Kim S, Kim S, Kim HS, Jung EM, An BS, Yang SY. One-touch embeddable microneedles for hair loss treatment. Int J Pharm 2025; 669:125020. [PMID: 39626847 DOI: 10.1016/j.ijpharm.2024.125020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 11/11/2024] [Accepted: 11/30/2024] [Indexed: 12/10/2024]
Abstract
With increasing clinical demands for painless and easy administration of medications, such as for hair loss, microneedles (MNs) have been widely exploited for facilitating drug permeation in a minimally invasive manner. However, precise dose control and long-term drug delivery without the infection risk through punctured holes have remained unresolved. Herein, we developed swellable microneedles (MNs) with an air-pocket structure, enabling shear-induced implantation inside the skin. The air-pocket MNs (AP-MNs) were prepared by one-step molding process with genipin-crosslinked gelatin solutions. This MN design induced mechanical difference following insertion due to selective hydration at the inserted MN tips, causing them to break at the interface between the swollen tip and the non-inserted column. The AP-MNs (80-90 %) were embedded into the skin and played a barrier function by tightly sealing punctured holes. Minoxidil (MXD) for hair loss treatment were quantitatively loaded in the AP-MNs depending on swellable tip heights, with 90 % of loaded MXD in the AP-MN tips released over 48 h. In animal studies, the MXD-loaded AP-MNs exhibited higher efficiency than topical application for hair loss treatment. These results indicate that the design of shear-induced embeddable MNs could provide a high-efficiency, convenient, safe, and potentially self-administered method for drug delivery.
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Affiliation(s)
- Keum-Yong Seong
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Min Jae Kim
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea; Institute for Future Earth, Pusan National University, Busan 46241, Republic of Korea
| | - Hyeseon Lee
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Sodam Kim
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea
| | - Semin Kim
- SNvia Co., Ltd., PNU AVEC, Busan 46285, Republic of Korea
| | - Hoon-Soo Kim
- Department of Dermatology, School of Medicine, Pusan National University, Busan 49241, Republic of Korea
| | - Eui-Man Jung
- Institute for Future Earth, Pusan National University, Busan 46241, Republic of Korea; Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea
| | - Beum-Soo An
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea.
| | - Seung Yun Yang
- Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Republic of Korea.
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Cui H, Fu LQ, Teng Y, He JJ, Shen YY, Bian Q, Wang TZ, Wang MX, Pang XW, Lin ZW, Zhu MG, Cai Y, Li YY, Chen JY, Mou XZ, Fan YB. Human Hair Follicle Mesenchymal Stem Cell-Derived Exosomes Attenuate UVB-Induced Photoaging via the miR-125b-5p/TGF-β1/Smad Axis. Biomater Res 2025; 29:0121. [PMID: 39807308 PMCID: PMC11725759 DOI: 10.34133/bmr.0121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 10/09/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025] Open
Abstract
Cutaneous photoaging, induced by chronic exposure to ultraviolet (UV) radiation, typically manifests as alterations in both the physical appearance and functional properties of the skin and may predispose individuals to cancer development. Recent studies have demonstrated the reparative potential of exosomes derived from mesenchymal stem cells in addressing skin damage, while specific reports highlight their efficacy in ameliorating skin photoaging. However, the precise role of exosomes derived from human hair follicle mesenchymal stem cells (HFMSC-Exos) in the context of cutaneous photoaging remains largely unexplored. We successfully isolated HFMSC-Exos using the ultracentrifugation technique. In cellular experiments, we assessed the migration of human dermal fibroblasts (HDFs) through scratch and transwell assays, evaluated the angiogenesis of human umbilical vein endothelial cells through angiogenesis assays, and examined the expression levels of collagen and matrix metalloproteinase 1 (MMP-1) using Western blotting and quantitative reverse transcription polymerase chain reaction. Furthermore, we established a nude mouse model of photoaging to observe wrinkle formation on the dorsal surface of the animals, as well as to assess dermal thickness and collagen fiber generation through histological staining. Ultimately, we performed RNA sequencing on skin tissues from mice before and after treatment to elucidate the relevant underlying mechanisms. Our findings revealed that HFMSC-Exos effectively enhanced the migration and proliferation of HDFs and upregulated the expressions of transforming growth factor-β1 (TGF-β1), p-Smad2/p-Smad3, collagen type 1, and collagen type 3 while concurrently down-regulating MMP-1 levels in HDFs. Additionally, mice in the HFMSC-Exo group showed quicker wrinkle healing and increased collagen production. HFMSC-Exos miR-125b-5p was demonstrated to reduce skin photoaging by increasing profibrotic levels via TGF-β1 expression. UV-irradiated HDFs and photoaged nude mouse skin showed low TGF-β1 expressions, whereas overexpression of TGF-β1 in HDFs increased collagen type 1, collagen type 3, and p-Smad2/p-Smad3 expressions while decreasing MMP-1 expression. HDFs overexpressing TGF-β1 produced more collagen and altered the Smad pathway. This study demonstrated, both in vitro and in vivo, that HFMSC-Exos increased collagen formation, promoted HDF cell proliferation and migration, and reversed the senescence of UV-irradiated HDFs. TGF-β1 was identified as a target of HFMSC-Exos miR-125b-5p, which controls photoaging via regulating the Smad pathway. The antiphotoaging capabilities of HFMSC-Exos may occur via the miR-125b-5p/TGF-β1/Smad axis, suggesting a promising therapeutic approach for treating skin photoaging.
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Affiliation(s)
- Hong Cui
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Luo-Qin Fu
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Yan Teng
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
| | - Jun-Jia He
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Ye-Yu Shen
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Qiong Bian
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Ting-Zhang Wang
- Key Laboratory of Microbiol Technology and Bioinformatics of Zhejiang Province,
Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Mei-Xia Wang
- Key Laboratory of Microbiol Technology and Bioinformatics of Zhejiang Province,
Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Xiang-Wei Pang
- Key Laboratory of Microbiol Technology and Bioinformatics of Zhejiang Province,
Zhejiang Institute of Microbiology, Hangzhou 310012, China
| | - Zhi-Wei Lin
- HealthRegen (Hangzhou) Biotechnology Co., Ltd, Hangzhou 310052, China
| | - Min-Gang Zhu
- Department of Dermatology,
The First People’s Hospital of Jiashan, Jiaxing 314100, China
| | - Yu Cai
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Yang-Yang Li
- Women’s Hospital,
Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Jin-Yang Chen
- Department of Dermatology,
The First People’s Hospital of Jiashan, Jiaxing 314100, China
| | - Xiao-Zhou Mou
- Clinical Research Institute, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, China
| | - Yi-Bin Fan
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital,
Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
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Gentile P, Garcovich S, Perego F, Arsiwala N, Yavuz MF, Pessei V, Pusceddu T, Zavan B, Arsiwala S. Autologous Micrografts Containing Nanovesicles, Exosomes, and Follicle Stem Cells in Androgenetic Alopecia: In Vitro and In Vivo Analysis Through a Multicentric, Observational, Evaluator-Blinded Study. Aesthetic Plast Surg 2025; 49:43-58. [PMID: 39453468 DOI: 10.1007/s00266-024-04439-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 10/01/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND The use of micrografts (MCGs) containing human follicle mesenchymal stem cells (HF-MSCs) is a hair loss (HL) treatment that needs to be standardized as seems to have promising effects on hair regrowth (HR-G) also thanks to the presence of extracellular vesicles (EVs). OBJECTIVES The study aims to report both the in vivo results, obtained in patients affected by androgenic alopecia (AGA) treated using MCGs, and in vitro analysis characterizing the EVs. METHODS A multicentric, retrospective, observational, evaluator-blinded study was conducted. Eighty-three AGA patients were initially enrolled [52 suffering from male pattern hair loss (MPHL) at stages I-III vertex by the Norwood-Hamilton scale and 31 suffering from female PHL (FPHL) at stages I-II by the Ludwig scale]. Sixty patients (20 females and 40 males) were treated and analyzed after exclusion and inclusion criteria assessment. The in vivo HR-G was evaluated through photography, physician's, and patient's global assessment scales, in addition to standardized photo-trichograms, during a follow-up for 1 year, while the in vitro analysis was performed through a quantitative, morphological, and dimensional characterization of the EVs population using transmission electron microscopy (TEM) and fluorescent microscopy. RESULTS A hair density (HD) increase of 28 ± 4 hairs/cm2 at T4 after 12 months in the targeted area (TA) of FPHL, compared with the baseline, was observed using computerized trichograms with a statistically significant difference (SSD) in hair regrowth (HR-G) (p = 0.0429). Regarding MPHL, an HD increase of 30 ± 5 hairs/cm2 at T4 after 12 months in the TA was observed with an SSD in HR-G (p = 0.0012). The presence of EVs and their interaction with the surrounding cellular population were demonstrated. CONCLUSIONS MCGs containing HF-MSCs and exosomes may fill in as a safe and viable alternative treatment against HL in mild and moderate degrees of AGA both in MPHL and in FPHL. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Pietro Gentile
- Plastic and Reconstructive Surgery, Department of Surgical Science, "Tor Vergata" University, 00133, Rome, Italy.
- Academy of International Regenerative Medicine & Surgery Societies (AIRMESS), 1201, Geneva, Switzerland.
- "Tor Vergata" University, Via Montpellier 1, 00173, Rome, Italy.
| | | | - Franco Perego
- School of Plastic, Reconstructive and Aesthetic Surgery, University of Padua, Padua, Italy
| | - Nazneen Arsiwala
- Renewderm Skin Hair Laser Aesthetics Centre and Masina Hospital Mumbai, Mumbai, India
| | | | - Valeria Pessei
- Department Chemistry, Biology, Biotechnology, University of Perugia, Perugia, Italy
- SHRO Italia Foundation ETS, via Sestriere 17, Candiolo (Turin), Italy
| | - Tommaso Pusceddu
- Department Translational Medicine, University of Ferrara, 44121, Ferrara, Italy
| | - Barbara Zavan
- Department Translational Medicine, University of Ferrara, 44121, Ferrara, Italy
| | - Shenaz Arsiwala
- Renewderm Skin Hair Laser Aesthetics Centre and Saifee Hospital, Masina Hospital Mumbai, Mumbai, India
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Kim J, Lee Y, Kim J, Park CW, Song H, Hong J, Lee S, Jung WH, Hong JH, Kim KH, Lee W. Conductive Bio-Harvesting Tonic (CBT) with an Anti-Dandruff Effect Enhances Hair Growth by Utilizing Naturally Generated Electric Energy during Human Activities. J Microbiol Biotechnol 2024; 34:2376-2384. [PMID: 39300961 PMCID: PMC11637866 DOI: 10.4014/jmb.2408.08014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 08/28/2024] [Indexed: 09/22/2024]
Abstract
Alopecia, while not life-threatening, significantly impacts mental health, identity, and self-esteem of those afflicted. Current pharmacological and surgical treatments often have side effects and are limited in their ability to regenerate hair follicles (HF). Therefore, effective solutions for alopecia remain elusive. We developed an innovative hair tonic capable of stimulating HF regeneration by harnessing abandoned electric energy generated during human activities, such as the frictional electric field from walking and the electric fields from electronic devices. We devised a convenient, non-volatile, and conductive hair tonic to capture these naturally occurring electric fields. We identified 6-pentyl-α-pyrone (6PP) from Trichoderma gamsii as an antifungal agent effective against the dandruff-associated fungus Malassezia that can influence alopecia and adopted it into our conductive bio-harvesting tonic (CBT). Testing on hair follicle dermal papilla cells (HFDPC) and SKH1 mice showed that CBT significantly enhanced HF proliferation and increased growth factors in vitro and in vivo. In SKH1 mice, application of CBT under electric stimulation visibly increased hair shaft length and follicle counts. Additionally, tests on actual human hair follicles demonstrated delayed hair follicle regression when electric stimulation and 6PP were applied. In conclusion, our innovative CBT offers a promising and convenient approach for improving hair growth and combating alopecia.
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Affiliation(s)
- Jisun Kim
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Yoonsuk Lee
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jungbum Kim
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Chai Won Park
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | | | - Jinkee Hong
- Barunbio Inc., Seoul 03722, Republic of Korea
- School of Chemical & Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea
| | - Sangmin Lee
- School of Mechanical Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Won Hee Jung
- Department of Systems Biotechnology, Chung-Ang University, Anseong 17546, Republic of Korea
| | - Joo-Hyun Hong
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ki Hyun Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Wonhwa Lee
- Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea
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11
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Luo X, Ni X, Zhi J, Jiang X, Bai R. Small molecule agents against alopecia: Potential targets and related pathways. Eur J Med Chem 2024; 276:116666. [PMID: 39002436 DOI: 10.1016/j.ejmech.2024.116666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/28/2024] [Accepted: 07/08/2024] [Indexed: 07/15/2024]
Abstract
Alopecia has emerged as a global concern, extending beyond the middle-aged and elderly population and increasingly affecting younger individuals. Despite its growing prevalence, the treatment options and effective drugs for alopecia remain limited due to the incomplete understanding of its underlying mechanisms. Therefore, it is urgent to explore the pathogenesis of alopecia and discover novel and safer therapeutic agents. This review provided an overview of the prevailing clinical disorders of alopecia, and the key pathways and targets involved in hair growth process. Additionally, it discusses FDA-approved drugs and clinical candidates for the treatment of alopecia, and explores small molecule compounds with anti-alopecia potential in the drug discovery phase. These endeavors are expected to provide researchers with valuable scientific insights and practical information for anti-alopecia drug discovery.
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Affiliation(s)
- Xinyu Luo
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-tumor Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Xinhua Ni
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-tumor Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Jia Zhi
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-tumor Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Xiaoying Jiang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-tumor Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China
| | - Renren Bai
- School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-tumor Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China.
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12
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Lee S, Ohn J, Kang BM, Hwang ST, Kwon O. Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles. J Adv Res 2024; 64:237-247. [PMID: 37972887 PMCID: PMC11464481 DOI: 10.1016/j.jare.2023.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 11/06/2023] [Accepted: 11/12/2023] [Indexed: 11/19/2023] Open
Abstract
INTRODUCTION Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. OBJECTIVES To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. METHODS The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. RESULTS During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs. CONCLUSIONS Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.
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Affiliation(s)
- Seunghee Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea
| | - Jungyoon Ohn
- Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea
| | - Bo Mi Kang
- Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea
| | | | - Ohsang Kwon
- Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
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13
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Oh HG, Jung M, Jeong SY, Kim J, Han SD, Kim H, Lee S, Lee Y, You H, Park S, Kim EA, Kim TM, Kim S. Improvement of androgenic alopecia by extracellular vesicles secreted from hyaluronic acid-stimulated induced mesenchymal stem cells. Stem Cell Res Ther 2024; 15:287. [PMID: 39256806 PMCID: PMC11389250 DOI: 10.1186/s13287-024-03906-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 08/27/2024] [Indexed: 09/12/2024] Open
Abstract
BACKGROUND Androgenetic alopecia (AGA) is a common form of hair loss. Androgens, such as testosterone and dihydrotestosterone, are the main causes of AGA. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can reduce AGA. However, preparing therapeutic doses of MSCs for clinical use is challenging. Induced pluripotent stem cell-derived MSCs (iMSCs) are homogenous and easily expandable, enabling scalable production of EVs. Hyaluronic acid (HA) can exert various functions including free radical scavenging, immune regulation, and cell migration. Herein, we examined whether hyaluronic acid (HA) stimulation of iMSCs could produce EVs with enhanced therapeutic outcomes for AGA. METHODS EVs were collected from iMSCs primed with HA (HA-iMSC-EVs) or without HA (iMSC-EVs). The characteristics of EVs were examined using dynamic light scattering, cryo-transmission electron microscopy, immunoblotting, flow cytometry, and proteomic analysis. In vitro, we compared the potential of EVs in stimulating the survival of hair follicle dermal papilla cells undergoing testosterone-mediated AGA. Additionally, the expression of androgen receptor (AR) and relevant growth factors as well as key proteins of Wnt/β-catenin signaling pathway (β-catenin and phosphorylated GSK3β) was analyzed. Subsequently, AGA was induced in male C57/BL6 mice by testosterone administration, followed by repeated injections of iMSC-EVs, HA-iMSC-EVs, finasteride, or vehicle. Several parameters including hair growth, anagen phase ratio, reactivation of Wnt/β-catenin pathway, and AR expression was examined using qPCR, immunoblotting, and immunofluorescence analysis. RESULTS Both types of EVs showed typical characteristics for EVs, such as size distribution, markers, and surface protein expression. In hair follicle dermal papilla cells, the mRNA levels of AR, TGF-β, and IL-6 increased by testosterone was blocked by HA-iMSC-EVs, which also contributed to the augmented expression of trophic genes related to hair regrowth. However, no notable changes were observed in the iMSC-EVs. Re-activation of Wnt/β-catenin was observed in HA-iMSC-EVs but not in iMSC-EVs, as shown by β-catenin stabilization and an increase in phosphorylated GSK3β. Restoration of hair growth was more significant in HA-iMSC-EVs than in iMSC-EVs, and was comparable to that in mice treated with finasteride. Consistently, the decreased anagen ratio induced by testosterone was reversed by HA-iMSC-EVs, but not by iMSC-EVs. An increased expression of hair follicular β-catenin protein, as well as the reduction of AR was observed in the skin tissue of AGA mice receiving HA-iMSC-EVs, but not in those treated with iMSC-EVs. CONCLUSIONS Our results suggest that HA-iMSC-EVs have potential to improve AGA by regulating growth factors/cytokines and stimulating AR-related Wnt/β-catenin signaling.
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Affiliation(s)
- Hyun Geun Oh
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Minyoung Jung
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Seon-Yeong Jeong
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Jimin Kim
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Sang-Deok Han
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Hongduk Kim
- Institute of Green Bio Science and Technology, Seoul National University, 1447 Pyeongchang Daero, Pyeongchang, Gangwon-do, 25354, Republic of Korea
| | - Seulki Lee
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Yejin Lee
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Haedeun You
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Somi Park
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Eun A Kim
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea
| | - Tae Min Kim
- Institute of Green Bio Science and Technology, Seoul National University, 1447 Pyeongchang Daero, Pyeongchang, Gangwon-do, 25354, Republic of Korea.
- Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang, Gangwon-do, 25354, Republic of Korea.
| | - Soo Kim
- R&D Center, Brexogen Inc., 3F, 9, Beobwon-ro 8-gil, Songpa-gu, Seoul, 05855, Republic of Korea.
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14
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Niu Y, Li Y, Gao C, Li W, Li L, Wang H, Shen W, Ge W. Melatonin promotes hair regeneration by modulating the Wnt/β-catenin signalling pathway. Cell Prolif 2024; 57:e13656. [PMID: 38773710 PMCID: PMC11503254 DOI: 10.1111/cpr.13656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 04/23/2024] [Accepted: 05/03/2024] [Indexed: 05/24/2024] Open
Abstract
Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/β-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/β-catenin signalling pathway revealed that MLT up-regulated the Wnt/β-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/β-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans.
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Affiliation(s)
- Yi‐Lin Niu
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Yu‐Kang Li
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Chen‐Xi Gao
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Wen‐Wen Li
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Li Li
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Han Wang
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Wei Shen
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
| | - Wei Ge
- College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of ShandongQingdao Agricultural UniversityQingdaoChina
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15
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Noguchi K, Inai T, Kuwana R. Chitinase 3-Like 1 and C-X-C motif chemokine ligand 5 proteins and the hair cycle. Arch Dermatol Res 2024; 316:523. [PMID: 39150635 DOI: 10.1007/s00403-024-03151-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 05/13/2024] [Accepted: 05/19/2024] [Indexed: 08/17/2024]
Abstract
Dermal papilla cells (DPCs) exhibit self-recovery ability, which may be involved in hair growth. Therefore, we tested whether DPCs subjected to temporary growth-inhibiting stress (testosterone, 17β-estradiol, mitomycin C, or undernutrition) treatments exhibit self-recovery behavior that can activate hair follicle growth, and examined the changes in cell proliferation capacity and gene expression. Related proteins were identified and their relationships with the hair cycle was examined using a mouse model. Recovery-period DPCs (i.e., from day 3 after loading) were subjected to microarray analysis to detect genetic variations common to each stress treatment. Co-culture of recovery-period DPCs and outer root sheath cells (ORSCs) confirmed the promotion of ORSC proliferation, suggesting that the activation of hair follicle growth is promoted via signal transduction. Chitinase 3-like 1 (CHI3L1) and C-X-C motif chemokine 5 (CXCL5) exhibited ORSC proliferation-promoting effects. Measurement of protein content in the skin during each phase of the hair cycle in mice revealed that CHI3L1 and CXCL5 secretion increased immediately after anagen transition. In a hair-loss mouse model treated with testosterone or 17β-estradiol, CHI3L1 and CXCL5 secretion was lower in treated telogen skin than in untreated skin. Our results suggest that CHI3L1 and CXCL5 secreted by recovery-state DPCs promote hair growth.
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Affiliation(s)
- Kazuma Noguchi
- Department of Research and Development, Fuji Sangyo Co., Ltd., Tamura-cho, Kagawa, Marugame-shi, 763-8603, Japan.
| | - Takanori Inai
- Department of Research and Development, Fuji Sangyo Co., Ltd., Tamura-cho, Kagawa, Marugame-shi, 763-8603, Japan
| | - Ryuichiro Kuwana
- Kuwana Dermatology Clinic, Ozucho, Kochi-shi, Kochi, 780-0915, Japan
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16
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Bejaoui M, Oliva Mizushima AK, Ngoc Linh T, Arimura T, Tominaga K, Isoda H. Triethylene Glycol Squalene Improves Hair Regeneration by Maintaining the Inductive Capacity of Human Dermal Papilla Cells and Preventing Premature Aging. ACS Pharmacol Transl Sci 2024; 7:2006-2022. [PMID: 39022356 PMCID: PMC11249624 DOI: 10.1021/acsptsci.4c00114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/25/2024] [Accepted: 05/28/2024] [Indexed: 07/20/2024]
Abstract
De novo hair follicle (HF) regeneration, achieved through the replenishment of the dermal papilla (DP), acknowledged as the principal orchestrator of the hair growth cycle, is emerging as a prospective therapeutic intervention for alopecia. Nonetheless, multiple attempts have shown that these cells lose key inductive properties when cultured in a two-dimensional (2D) monolayer, leading to precocious senescence engendered by oxidative stress and inflammatory processes. Consequently, the three-dimensional (3D) spheroid technique is presently widely employed for DP cell culture. Nevertheless, substantiating the regenerative potential of these cells within the hair follicle (HF) milieu remains a challenge. In this current study, we aim to find a new approach to activate the inductive properties of DP cells. This involves the application of hair-growth-stimulating agents that not only exhibit concurrent protective efficacy against the aging process but also induce HF regeneration. To achieve this objective, we initially synthesized a novel highly amphiphilic derivative derived from squalene (SQ), named triethylene glycol squalene (Tri-SQ). Squalene itself is a potent antioxidant and anti-inflammatory compound traditionally employed as a drug carrier for alopecia treatment. However, its application is limited due to its low solubility. Subsequently, we applied this newly synthesized derivative to DP cells. The data obtained demonstrated that the derivative exhibits robust antioxidant and anti-inflammatory activities while concurrently promoting the expression of genes associated with hair growth. Moreover, to further assess the hair regrowth inductive properties of DP cells, we cultured the cells and treated them with Tri-SQ within a 3D spheroid system. Subsequently, these treated cells were injected into the previously depilated dorsal area of six-week-old male C57BL/6 mice. Results revealed that 20 days postinjection, a complete regrowth of hair in the previously hairless area, particularly evident in the case of 3D spheroids treated with the derivative, was observed. Additionally, histological and molecular analyses demonstrated an upregulation of markers associated with hair growth and a concurrent decrease in aging hallmarks, specifically in the 3D spheroids treated with the compound. In summary, our approach, which involves the treatment of Tri-SQ combined with a 3D spheroid system, exhibited a notably robust stimulating effect. This effect was observed in the induction of inductive properties in DP cells, leading to HF regeneration, and concurrently, it demonstrated an inhibitory effect on cellular and follicular aging.
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Affiliation(s)
- Meriem Bejaoui
- Open
Innovation Laboratory for Food and Medicinal Resource Engineering
(FoodMed-OIL), National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba City 305-8568, Japan
- Alliance
for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba City 305-0006, Japan
- Research
and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba
City 305-0006, Japan
| | - Aprill Kee Oliva Mizushima
- Alliance
for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba City 305-0006, Japan
- Research
and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba
City 305-0006, Japan
| | - Tran Ngoc Linh
- Open
Innovation Laboratory for Food and Medicinal Resource Engineering
(FoodMed-OIL), National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba City 305-8568, Japan
| | - Takashi Arimura
- Open
Innovation Laboratory for Food and Medicinal Resource Engineering
(FoodMed-OIL), National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba City 305-8568, Japan
| | - Kenichi Tominaga
- Open
Innovation Laboratory for Food and Medicinal Resource Engineering
(FoodMed-OIL), National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba City 305-8568, Japan
| | - Hiroko Isoda
- Open
Innovation Laboratory for Food and Medicinal Resource Engineering
(FoodMed-OIL), National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba City 305-8568, Japan
- Alliance
for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba City 305-0006, Japan
- Research
and Development Center for Tailor-Made QOL Program, University of Tsukuba, Tsukuba
City 305-0006, Japan
- Faculty
of Life and Environmental Sciences, University
of Tsukuba, Tsukuba City 305-0006, Japan
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Marinho PA, Jeong G, Shin SH, Kim SN, Choi H, Lee SH, Park BC, Hong YD, Kim HJ, Park WS. The development of an in vitrohuman hair follicle organoid with a complexity similar to that in vivo. Biomed Mater 2024; 19:025041. [PMID: 38324888 DOI: 10.1088/1748-605x/ad2707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 02/07/2024] [Indexed: 02/09/2024]
Abstract
In vitrohair follicle (HF) models are currently limited toex vivoHF organ cultures (HFOCs) or 2D models that are of low availability and do not reproduce the architecture or behavior of the hair, leading to poor screening systems. To resolve this issue, we developed a technology for the construction of a humanin vitrohair construct based on the assemblage of different types of cells present in the hair organ. First, we demonstrated that epithelial cells, when isolatedin vitro, have similar genetic signatures regardless of their dissection site, and their trichogenic potential is dependent on the culture conditions. Then, using cell aggregation techniques, 3D spheres of dermal papilla (DP) were constructed, and subsequently, epithelial cells were added, enabling the production and organization of keratins in hair, similar to what is seenin vivo. These reconstructed tissues resulted in the following hair compartments: K71 (inner root-sheath), K85 (matrix region), K75 (companion layer), and vimentin (DP). Furthermore, the new hair model was able to elongate similarly toex vivoHFOC, resulting in a shaft-like shape several hundred micrometers in length. As expected, when the model was exposed to hair growth enhancers, such as ginseng extract, or inhibitors, such as TGF-B-1, significant effects similar to thosein vivowere observed. Moreover, when transplanted into skin biopsies, the new constructs showed signs of integration and hair bud generation. Owing to its simplicity and scalability, this model fully enables high throughput screening of molecules, which allows understanding of the mechanism by which new actives treat hair loss, finding optimal concentrations, and determining the synergy and antagonism among different raw materials. Therefore, this model could be a starting point for applying regenerative medicine approaches to treat hair loss.
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Affiliation(s)
| | - Gyusang Jeong
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Seung Hyun Shin
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Su Na Kim
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Hyeongwon Choi
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Sung Hoon Lee
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Byung Cheol Park
- Department of Dermatology, College of Medicine, Dankook University, Cheonan-si, Republic of Korea
| | - Yong Deog Hong
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Hyoung-June Kim
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
| | - Won-Seok Park
- AMOREPACIFIC Research and Innovation Center, Yongin-si, Republic of Korea
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18
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Li C, He X, Wu Y, Li J, Zhang R, An X, Yue Y. Single-Cell Transcriptome Sequence Profiling on the Morphogenesis of Secondary Hair Follicles in Ordos Fine-Wool Sheep. Int J Mol Sci 2024; 25:584. [PMID: 38203755 PMCID: PMC10779399 DOI: 10.3390/ijms25010584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 12/22/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
The Ordos fine-wool sheep is a high-quality breed in China that produces superior natural textiles and raw materials such as wool and lamb meat. However, compared to the Australian Merino sheep, there is still a gap in terms of the wool fiber fineness and wool yield. The hair follicle is the main organ that controls the type of wool fiber, and the morphological changes in the secondary hair follicle are crucial in determining wool quality. However, the process and molecular mechanisms of hair follicle morphogenesis in Ordos fine-wool sheep are not yet clear. Therefore, analyzing the molecular mechanisms underlying the process of follicle formation is of great significance for improving the fiber diameter and wool production of Ordos fine-wool sheep. The differential expressed genes, APOD, POSTN, KRT5, and KRT15, which related to primary hair follicles and secondary hair follicles, were extracted from the dermal papillae. Based on pseudo-time analysis, the differentiation trajectories of dermal lineage cells and epidermal lineage cells in the Ordos fine-wool sheep were successfully constructed, providing a theoretical basis for breeding research in Ordos fine-wool sheep.
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Affiliation(s)
- Chenglan Li
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xue He
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Yi Wu
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Jianye Li
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Rui Zhang
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xuejiao An
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Yaojing Yue
- Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (C.L.)
- Sheep Breeding Engineering Technology Research Center, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
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19
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Zhu N, Yan J, Gu W, Yang Q, Lin E, Lu S, Cai B, Xia B, Liu X, Lin C. Dermal papilla cell-secreted biglycan regulates hair follicle phase transit and regeneration by activating Wnt/β-catenin. Exp Dermatol 2024; 33:e14969. [PMID: 37967213 DOI: 10.1111/exd.14969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 09/06/2023] [Accepted: 10/19/2023] [Indexed: 11/17/2023]
Abstract
Alopecia is a prevalent problem of cutaneous appendages and lacks effective therapy. Recently, researchers have been focusing on mesenchymal components of the hair follicle, i.e. dermal papilla cells, and we previously identified biglycan secreted by dermal papilla cells as the key factor responsible for hair follicle-inducing ability. In this research, we hypothesized biglycan played an important role in hair follicle cycle and regeneration through regulating the Wnt signalling pathway. To characterize the hair follicle cycle and the expression pattern of biglycan, we observed hair follicle morphology in C57BL/6 mice on Days 0, 3, 5, 12 and 18 post-depilation and found that biglycan is highly expressed at both mRNA and protein levels throughout anagen in HFs. To explore the role of biglycan during the phase transit process and regeneration, local injections were administered in C57BL/6 and nude mice. Results showed that local injection of biglycan in anagen HFs delayed catagen progression and involve activating the Wnt/β-catenin signalling pathway. Furthermore, local injection of biglycan induced HF regeneration and up-regulated expression of key Wnt factors in nude mice. In addition, cell analyses exhibited biglycan knockdown inactivated the Wnt signalling pathway in early-passage dermal papilla cell, whereas biglycan overexpression or incubation activated the Wnt signalling pathway in late-passage dermal papilla cells. These results indicate that biglycan plays a critical role in regulating HF cycle transit and regeneration in a paracrine and autocrine fashion by activating the Wnt/β-catenin signalling pathway and could be a potential treatment target for hair loss diseases.
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Affiliation(s)
- Ningxia Zhu
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Junping Yan
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Weifan Gu
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Qilin Yang
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - En Lin
- Department of Histology and Embryology, Shantou University Medical College, Shantou, People's Republic of China
| | - Siyue Lu
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Bozhi Cai
- Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, Shantou, People's Republic of China
| | - Bin Xia
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Xin Liu
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, People's Republic of China
| | - Changmin Lin
- Department of Histology and Embryology, Shantou University Medical College, Shantou, People's Republic of China
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20
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Li J, Tian G, Wang X, Tang H, Liu Y, Guo H, Wang C, Chen Y, Yang Y. Effects of short photoperiod on cashmere growth, hormone concentrations and hair follicle development-related gene expression in cashmere goats. JOURNAL OF APPLIED ANIMAL RESEARCH 2023. [DOI: 10.1080/09712119.2022.2153853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Junda Li
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Guangjie Tian
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Xingtao Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Hongyu Tang
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Yuyang Liu
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Hongran Guo
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Chunxin Wang
- Jilin Academy of Agriculture Sciences, Gongzhuling, People’s Republic of China
| | - Yulin Chen
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
| | - Yuxin Yang
- College of Animal Science and Technology, Northwest A&F University, Yangling, People’s Republic of China
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21
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Zheng Q, Ye N, Bao P, Wang T, Ma C, Chu M, Wu X, Kong S, Guo X, Liang C, Pan H, Yan P. Interpretation of the Yak Skin Single-Cell Transcriptome Landscape. Animals (Basel) 2023; 13:3818. [PMID: 38136855 PMCID: PMC10741061 DOI: 10.3390/ani13243818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
The morphogenesis of hair follicle structure is accompanied by the differentiation of skin tissue. Mammalian coats are produced by hair follicles. The formation of hair follicles requires signal transmission between the epidermis and dermis. However, knowledge of the transcriptional regulatory mechanism is still lacking. We used single-cell RNA sequencing to obtain 26,573 single cells from the scapular skin of yaks at hair follicle telogen and anagen stages. With the help of known reference marker genes, 11 main cell types were identified. In addition, we further analyzed the DP cell and dermal fibroblast lineages, drew a single-cell map of the DP cell and dermal fibroblast lineages, and elaborated the key genes, signals, and functions involved in cell fate decision making. The results of this study provide a very valuable resource for the analysis of the heterogeneity of DP cells and dermal fibroblasts in the skin and provide a powerful theoretical reference for further exploring the diversity of hair follicle cell types and hair follicle morphogenesis.
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Affiliation(s)
- Qingbo Zheng
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Na Ye
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Pengjia Bao
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Tong Wang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Chaofan Ma
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Min Chu
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Xiaoyun Wu
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Siyuan Kong
- Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China;
| | - Xian Guo
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Chunnian Liang
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
| | - Heping Pan
- Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China
| | - Ping Yan
- Key Laboratory of Animal Genetics and Breeding on Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China; (Q.Z.); (N.Y.); (P.B.); (T.W.); (C.M.); (M.C.); (X.W.); (X.G.); (C.L.)
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
- Institute of Western Agriculture, The Chinese Academy of Agricultural Sciences, Changji 831100, China
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22
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Kwack MH, Hamida OB, Kim MK, Kim MK, Sung YK. Establishment and characterization of matched immortalized human frontal and occipital scalp dermal papilla cell lines from androgenetic alopecia. Sci Rep 2023; 13:21421. [PMID: 38049592 PMCID: PMC10696020 DOI: 10.1038/s41598-023-48942-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 12/01/2023] [Indexed: 12/06/2023] Open
Abstract
Androgenetic alopecia (AGA), also known as male pattern baldness, is a common hair loss condition influenced by genetic and hormonal factors. Variations in gene expression and androgen responsiveness have been observed between the frontal and occipital regions of AGA patients. However, obtaining and cultivating frontal hair follicles is challenging. Therefore, no matched frontal and occipital dermal papilla (DP) cell lines have been reported yet. This study aimed to establish matched immortalized human frontal and occipital scalp DP cell lines from AGA patients. Simian virus 40 large T antigen (SV40T-Ag) and human telomerase reverse transcriptase (hTERT) were introduced into primary human DP cells. The obtained cell lines were characterized by assessing their gene expression patterns, androgen receptor (AR) levels, and the presence of 5-alpha reductase (5αR). Additionally, we examined their response to dihydrotestosterone (DHT) and evaluated cell viability. The conditioned medium from the frontal DP cell line inhibited human hair follicle growth, leading to reduced keratinocyte proliferation and increased apoptosis. Furthermore, when the cells were cultured in a 3D environment mimicking in vivo conditions, the 3D cultured frontal DP cell line exhibited weaker sphere aggregation than the occipital DP cell line due to the increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP9. Additionally, the expression of DP signature genes was inhibited in the 3D cultured frontal DP cell line. These matched frontal and occipital DP cell lines hold significant potential as valuable resources for research on hair loss. Their establishment allows us to investigate the differences between frontal and occipital DP cells, contributing to a better understanding of the molecular mechanisms underlying AGA. Furthermore, these cell lines may be valuable for developing targeted therapeutic approaches for hair loss conditions.
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Affiliation(s)
- Mi Hee Kwack
- Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea.
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu, Korea.
| | - Ons Ben Hamida
- Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea
| | - Min Kyu Kim
- Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea
| | - Moon Kyu Kim
- Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea
- Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Young Kwan Sung
- Department of Immunology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea
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23
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Li J, Zhao B, Zhang X, Dai Y, Yang N, Bao Z, Chen Y, Liu Y, Wu X. Establishment and functional characterization of immortalized rabbit dermal papilla cell lines. Anim Biotechnol 2023; 34:4050-4059. [PMID: 37652434 DOI: 10.1080/10495398.2023.2252861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Hair follicle (HF) undergo periodic growth and development in mammals, which regulated by dermal papilla cells (DPCs) are reported to play an important role in HF morphogenesis and development. However, primary DPCs have low proliferative activity, age quickly, and fresh cell isolation is both time-consuming and laborious. In this study, we introduced the SV40 large T antigen (SV40T) into dissociated early passage rabbit vibrissae DPCs with lentiviral vectors and established seven immortalized DPC lines (R-1, R-2, R-3, R-4, R-5, R-6 and R-7). These cell lines displayed early passage morphology and high alkaline phosphatase activity. RT-PCR and immunofluorescence staining showed that all the immortalized cell lines expressed the DPC markers (α-SMA, IGF1, ALPL, FGF2, BMP2 and TGFβ2), but α-SMA was only expressed well in R-3, R-4, and R-7. Furthermore, it was found that R-7 was the only line to survive beyond 50 passages. Compared to melanoma cells, R-7 did not undergo malignant transformation. Karyotyping and cell growth viability analysis illustrated that the R-7 cell line preserved the basic characteristics of primary DPCs. The R-7 DPCs established have potential application for future hair research. The study provides the theoretical basis in the cell research of HF growth and development.
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Affiliation(s)
- Jiali Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Bohao Zhao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Xiyu Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yingying Dai
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Naisu Yang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhiyuan Bao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yang Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yan Liu
- Animal Husbandry and Veterinary Research Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China
| | - Xinsheng Wu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
- Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu, China
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24
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Sumathy B, Velayudhan S. Fabrication and evaluation of a bi-layered gelatin based scaffold with arrayed micro-pits for full-thickness skin construct. Int J Biol Macromol 2023; 251:126360. [PMID: 37591428 DOI: 10.1016/j.ijbiomac.2023.126360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/17/2023] [Accepted: 08/14/2023] [Indexed: 08/19/2023]
Abstract
There is an unmet need for a reliable and reproducible method for incorporating hair follicle derived stem cells in tissue engineered skin models to reconstitute hair follicles. This study discloses a novel method for introducing hair follicle derived stem cells in microneedle embossed micro-pits of a bilayer skin equivalent fabricated from a gelatin based scaffold. The microneedles are hard and strong enough to penetrate the upper layer of the bilayer gelatin based scaffold that corresponds to the epidermis and permeates down to lower layer that corresponds to dermal layer. This strategic location will mimic the natural niche of hair follicle stem cells for picking up signals from both the epidermis and dermis. Hair follicle stem cells are trapped in to these micro-pits by vacuum assisted cell seeding. The bilayer system consists of two distinct electrospun layers in a single processing step, representing outer epidermal layer and inner dermal layer with hair follicle stem cells in embedded pits, resulting in the formation of a closed representation of a complete skin.
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Affiliation(s)
- Babitha Sumathy
- Department of Tissue Engineering and Regeneration Technologies, Department of Applied Biology, Biomedical Technology wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 012, India.
| | - Shiny Velayudhan
- Division of Dental Products, Department of Biomaterials Science and Technology, Biomedical Technology wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695 012, India.
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25
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Zhang G, Xu J, Zhang Y, Yang S, Jiang H. Expression of miRNA-1-3p and its target gene in hair follicle cycle development of Liaoning Cashmere goat. Anim Biotechnol 2023; 34:1937-1942. [PMID: 35443150 DOI: 10.1080/10495398.2022.2058519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
MicroRNA exerts an important regulatory role in almost all the biological process, including hair follicle development in Liaoning Cashmere goat. In order to improve the Cashmere performance of goat, the regulatory role of microRNA in hair follicle cycle has drawn hotspot attention. However, the molecular mechanisms of miRNA-1-3p involved in hair follicle development are poorly understood. In this study, we found that miRNA-1-3p was less expressed in anagen stage of hair follicle cycle of Cashmere goat than that in telogen stage by using RT-qPCR and immunoblotting analysis, in contrast to the expression pattern of FGF14. The Dual-Luciferase reporter assay was employed to verify the relationship between miRNA-1-3p and FGF14. The results showed that miRNA-1-3p specifically binds to the 3'UTR of FGF14 mRNA, and FGF14 is the target gene of miR-1-3p. In conclusion, this study shows that miRNA-1-3p may regulate hair follicle development in Liaoning Cashmere goats by targeting FGF14.
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Affiliation(s)
- Guishan Zhang
- School of Public Health, Jilin Medical University, Jilin, Jilin Province, China
| | - Jing Xu
- School of Basic Medical Sciences, Jilin Medical University, Jilin, Jilin Province, China
| | - Yingnan Zhang
- School of Public Health, Jilin Medical University, Jilin, Jilin Province, China
| | - Shubao Yang
- School of Basic Medical Sciences, Jilin Medical University, Jilin, Jilin Province, China
| | - Huaizhi Jiang
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin Province, China
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Hwang SB, Park HJ, Lee BH. Collagen Hydrolysate from the Scales of Mozambique Tilapia ( Oreochromis mossambicus) Improve Hair and Skin Health by Alleviating Oxidative Stress and Inflammation and Promoting Hair Growth and Extracellular Matrix Factors. Mar Drugs 2023; 21:475. [PMID: 37755088 PMCID: PMC10533131 DOI: 10.3390/md21090475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/24/2023] [Accepted: 08/28/2023] [Indexed: 09/28/2023] Open
Abstract
Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH extracted from Mozambique tilapia (Oreochromis mossambicus) scales on hair and skin using in vitro and in vivo models. Human dermal papilla cells (hDPCs) were used for antioxidant and gene expression analyses, while C57BL/6 mice were orally administered CH for six weeks to assess hair growth patterns. The mice were divided into four groups: negative control (NC; distilled water), positive control (PC; 1 mg/kg finasteride), CH500 (500 mg/kg BW CH), and CH1000 (1000 mg/kg BW CH). CH mitigated catalase activity reduction in hDPCs, increased IGF-1 and VEGF levels, and decreased TGF-β1, TNF-α, and IL-1β expression. In vivo, CH treatment improved hair growth index, length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage. Moreover, CH up-regulated IGF-1, VEGF, Elastin, and HAS2 mRNA expression while down-regulating TNF-α and IL-1β. CH enhanced hair shine, growth, and skin health while alleviating inflammation. These findings demonstrate the potential of CH in alleviating oxidative stress, promoting hair growth, and enhancing skin health, both in vitro and in vivo. Fish-derived CH offers a cost-effective and bioavailable option for improving hair and skin health.
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Affiliation(s)
| | | | - Bog-Hieu Lee
- Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea; (S.B.H.); (H.J.P.)
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Sibony-Benyamini H, Aamar E, Enshell-Seijffers D. Hdac1 and Hdac2 regulate the quiescent state and survival of hair-follicle mesenchymal niche. Nat Commun 2023; 14:4820. [PMID: 37563109 PMCID: PMC10415406 DOI: 10.1038/s41467-023-40573-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/02/2023] [Indexed: 08/12/2023] Open
Abstract
While cell division is essential for self-renewal and differentiation of stem cells and progenitors, dormancy is required to maintain the structure and function of the stem-cell niche. Here we use the hair follicle to show that during growth, the mesenchymal niche of the hair follicle, the dermal papilla (DP), is maintained quiescent by the activity of Hdac1 and Hdac2 in the DP that suppresses the expression of cell-cycle genes. Furthermore, Hdac1 and Hdac2 in the DP promote the survival of DP cells throughout the hair cycle. While during growth and regression this includes downregulation of p53 activity and the control of p53-independent programs, during quiescence, this predominantly involves p53-independent mechanisms. Remarkably, Hdac1 and Hdac2 in the DP during the growth phase also participate in orchestrating the hair cycle clock by maintaining physiological levels of Wnt signaling in the vicinity of the DP. Our findings not only provide insight into the molecular mechanism that sustains the function of the stem-cell niche in a persistently changing microenvironment, but also unveil that the same mechanism provides a molecular toolbox allowing the DP to affect and fine tune the microenvironment.
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Affiliation(s)
- Hadas Sibony-Benyamini
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar Ilan University, 8 Henrietta Szold, Safed, Israel
| | - Emil Aamar
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar Ilan University, 8 Henrietta Szold, Safed, Israel
| | - David Enshell-Seijffers
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar Ilan University, 8 Henrietta Szold, Safed, Israel.
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28
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Yue Z, Liu M, Zhang B, Li F, Li C, Chen X, Li F, Liu L. Vitamin A regulates dermal papilla cell proliferation and apoptosis under heat stress via IGF1 and Wnt10b signaling. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 262:115328. [PMID: 37562175 DOI: 10.1016/j.ecoenv.2023.115328] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 07/11/2023] [Accepted: 08/02/2023] [Indexed: 08/12/2023]
Abstract
Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P < 0.001) and inhibited the apoptosis of DPCs (P < 0.01). VA decreased the proportion of DPCs in G0/G1 stage of the cell cycle under HS along with the expression of caspase 3, heat shock protein 70 (HSP70), and microRNA 195 (miR-195) (P < 0.05). VA also activated the insulin-like growth factor 1 (IGF1) and Wnt10b/β-catenin signaling pathways. The results of the dual luciferase reporter assay showed that IGF1 expression was modulated by miR-195-5p. Over-expression of miR-195-5p in DPCs with HS+VA treatment significantly reduced cell viability and IGF1 signaling (P < 0.01) and increased apoptosis (P < 0.01) compared with the HS+VA group. The positive effects of VA on proliferation and apoptosis of DPCs under HS were significantly attenu-ated by blocking Wnt10b and β-catenin signaling with IWP-2 and XAV-939, respectively. These results demonstrate that VA can promote hair follicle development following HS via modulation of miR-195/IGF1 and Wnt10b/β-catenin signaling pathways.
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Affiliation(s)
- Zhengkai Yue
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Mengqi Liu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Bin Zhang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Fan Li
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Chenyang Li
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Xiaoyang Chen
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China
| | - Fuchang Li
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China.
| | - Lei Liu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Prov-ince), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Biotechnol-ogy and Disease Control and Prevention, Department of Animal Science, Shandong Agricultural University, Taian, Shandong 271018, China.
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Morkuzu S, McLennan AL, Kanapathy M, Mosahebi A. Use of Activated Platelet-Rich Plasma (A-PRP) on Alopecia: A Systematic Review and Meta-Analysis. Aesthet Surg J 2023; 43:NP631-NP649. [PMID: 36943284 DOI: 10.1093/asj/sjad073] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 03/23/2023] Open
Abstract
Alopecia affects perceptions of age, beauty, success, and adaptability. Hair loss can be caused by genetic, physiological, environmental, and immunologic factors. The current treatment for alopecia is varied. This systematic review and meta-analysis evaluates activated platelet rich plasma (A-PRP) for alopecia treatment. The objective of this review was to assess the clinical efficacy and safety of A-PRP injections in alopecia patients. We compared the safety, limitations, and outcomes of A-PRP use with those of previous research on alopecia. We searched PubMed, EMBASE, the Cochrane Database, and Google Scholar for relevant articles. We included all primary clinical studies involving patients that evaluated A-PRP. Twenty-nine articles, which included 864 patients, met the eligibility criteria and were analyzed for qualitative review. Our review found 27 studies that indicated A-PRP was significantly effective in treating alopecia, especially for improving hair density before and after therapy (n = 184, mean difference [MD] = 46.5, I2 = 88%, 95% CI: 29.63, 63.37, P < .00001), as well as when comparison was made between treatment and control groups (n = 88, MD = 31.61, I2 = 80%, 95% CI: 6.99, 56.22, P = .01), and of terminal hair density between treatment and control groups (n = 55, MD = 26.03, I2 = 25%, 95% CI: 8.08, 43.98, P = .004); hair counts after therapy (n = 85, MD = 12.79, I2 = 83%, 95% CI: -5.53, 31.12, P = .0006); promoting hair regrowth; folliculogenesis; reducing hair loss; combining with follicular unit extraction (FUE) surgery; and initiating the hair cycle. Two studies did not report significant results. This is the first systematic review and meta-analysis of A-PRP as a treatment option for alopecia. A-PRP appears to be a promising and safe method for treating alopecia. LEVEL OF EVIDENCE: 4
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Abreu CM, Lago MEL, Pires J, Reis RL, da Silva LP, Marques AP. Gellan gum-based hydrogels support the recreation of the dermal papilla microenvironment. BIOMATERIALS ADVANCES 2023; 150:213437. [PMID: 37116455 DOI: 10.1016/j.bioadv.2023.213437] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 03/10/2023] [Accepted: 04/17/2023] [Indexed: 04/30/2023]
Abstract
The dermal papilla (DP), a specialized compartment within the hair follicle, regulates hair growth. However, human DP cells rapidly lose their inductivity in 2D-culture given the loss of positional and microenvironmental cues. Spheroids have been capable of recreating the 3D intercellular organization of DP cells, however, DP cell-matrix interactions are poorly represented. Considering the specific nature of the DP's extracellular matrix (ECM), we functionalized gellan gum (GG) with collagen IV-(HepIII) or fibronectin-(cRGDfC) derived peptide sequences to generate a 3D environment in which the phenotype and physiological functions of DP cells are restored. We further tuned the stiffness of the microenvironments by varying GG amount. Biomimetic peptides in stiffer hydrogels promoted the adhesion of DP cells, while each peptide and amount of polymer independently influenced the type and quantity of ECM proteins deposited. Furthermore, although peptides did not seem to have an influence, stiffer hydrogels improved the inductive capacity of DP cells after short term culture. Interestingly, independently of the peptide, these hydrogels supported the recapitulation of basic hair morphogenesis-like events when incorporated in an organotypic human skin in vitro model. Our work demonstrates that tailored GG hydrogels support the generation of a microenvironment in which both cell-ECM and cell-cell interactions positively influence DP cells towards the creation of an artificial DP.
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Affiliation(s)
- Carla M Abreu
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Manuela E L Lago
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Joana Pires
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Lucília P da Silva
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Alexandra P Marques
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
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Cold atmospheric microwave plasma (CAMP) stimulates dermal papilla cell proliferation by inducing β-catenin signaling. Sci Rep 2023; 13:3089. [PMID: 36813838 PMCID: PMC9947002 DOI: 10.1038/s41598-023-30122-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 02/16/2023] [Indexed: 02/24/2023] Open
Abstract
Hair loss or alopecia is an unpleasant symptom that exacerbates an individual's self-esteem and requires appropriate treatment. The Wnt/β-catenin signaling is a central pathway that promotes dermal papilla induction and keratinocyte proliferation during hair follicle renewal. GSK-3β inactivated by its upstream Akt and ubiquitin-specific protease 47 (USP47) has been shown to inhibit β-catenin degradation. The cold atmospheric microwave plasma (CAMP) is microwave energy enriched with mixtures of radicals. CAMP has been reported to have antibacterial and antifungal activities with wound healing activity against skin infection; however, the effect of CAMP on hair loss treatment has not been reported. We aimed to investigate the effect of CAMP on promoting hair renewal in vitro and to elucidate the molecular mechanism, targeting β-catenin signaling and YAP/TAZ, the co-activators in the Hippo pathway, in human dermal papilla cells (hDPCs). We also evaluated plasma effects on the interaction between hDPCs and HaCaT keratinocytes. The hDPCs were treated with plasma-activating media (PAM) or gas-activating media (GAM). The biological outcomes were determined by MTT assay, qRT-PCR, western blot analysis, immunoprecipitation, and immunofluorescence. We found that β-catenin signaling and YAP/TAZ were significantly increased in PAM-treated hDPCs. PAM treatment also induced β-catenin translocation and inhibited β-catenin ubiquitination by activating Akt/GSK-3β signaling and upregulating USP47 expression. In addition, hDPCs were more aggregated with keratinocytes in PAM-treated cells compared with control. HaCaT cells cultured in a conditioned medium derived from PAM-treated hDPCs exhibited an enhancing effect on activating YAP/TAZ and β-catenin signaling. These findings suggested that CAMP may be a new therapeutic alternative for alopecic treatment.
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32
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Andl T, Zhou L, Zhang Y. The dermal papilla dilemma and potential breakthroughs in bioengineering hair follicles. Cell Tissue Res 2023; 391:221-233. [PMID: 36562864 PMCID: PMC9898212 DOI: 10.1007/s00441-022-03730-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
The generation and growing of de novo hair follicles is the most daring hair replacement approach to treat alopecia. This approach has been explored at least since the 1960s without major success. Latest in the 1980s, the realization that the mesenchymal compartment of hair follicles, the dermal papilla (DP), is the crucial signaling center and element required for fulfilling this vision of hair follicle engineering, propelled research into the fibroblasts that occupy the DP. However, working with DP fibroblasts has been stubbornly frustrating. Decades of work in understanding the nature of DP fibroblasts in vitro and in vivo have led to the appreciation that hair follicle biology is complex, and the dermal papilla is an enigma. Functional DP fibroblasts tend to aggregate in 2D culture, while impaired DP cells do not. This fact has stimulated recent approaches to overcome the hurdles to DP cell culture by mimicking their natural habitat, such as growing DP fibroblasts in three dimensions (3D) by their self-aggregation, adopting 3D matrix scaffold, or bioprinting 3D microstructures. Furthermore, including keratinocytes in the mix to form hair follicle-like composite structures has been explored but remains a far cry from a useful and affordable method to generate human hair follicles in sufficient quantity and quality in a practical time frame for patients. This suggests that the current strategies may have reached their limitations in achieving successful hair follicle bioengineering for clinical applications. Novel approaches are required to overcome these barriers, such as focusing on embryonic cell types and processes in combination with emerging techniques.
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Affiliation(s)
- Thomas Andl
- Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA
| | - Linli Zhou
- Division of Pharmaceutical Science, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA
| | - Yuhang Zhang
- Division of Pharmaceutical Science, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA.
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Colin-Pierre C, El Baraka O, Danoux L, Bardey V, André V, Ramont L, Brézillon S. Regulation of stem cell fate by HSPGs: implication in hair follicle cycling. NPJ Regen Med 2022; 7:77. [PMID: 36577752 PMCID: PMC9797564 DOI: 10.1038/s41536-022-00267-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 11/30/2022] [Indexed: 12/29/2022] Open
Abstract
Heparan sulfate proteoglycans (HSPGs) are part of proteoglycan family. They are composed of heparan sulfate (HS)-type glycosaminoglycan (GAG) chains covalently linked to a core protein. By interacting with growth factors and/or receptors, they regulate numerous pathways including Wnt, hedgehog (Hh), bone morphogenic protein (BMP) and fibroblast growth factor (FGF) pathways. They act as inhibitor or activator of these pathways to modulate embryonic and adult stem cell fate during organ morphogenesis, regeneration and homeostasis. This review summarizes the knowledge on HSPG structure and classification and explores several signaling pathways regulated by HSPGs in stem cell fate. A specific focus on hair follicle stem cell fate and the possibility to target HSPGs in order to tackle hair loss are discussed in more dermatological and cosmeceutical perspectives.
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Affiliation(s)
- Charlie Colin-Pierre
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France.
- BASF Beauty Care Solutions France SAS, Pulnoy, France.
| | | | - Louis Danoux
- BASF Beauty Care Solutions France SAS, Pulnoy, France
| | | | - Valérie André
- BASF Beauty Care Solutions France SAS, Pulnoy, France
| | - Laurent Ramont
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France
- CHU de Reims, Service Biochimie-Pharmacologie-Toxicologie, Reims, France
| | - Stéphane Brézillon
- Université de Reims Champagne-Ardenne, SFR CAP-Santé (FED 4231), Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France
- CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire-MEDyC, Reims, France
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Zheng Q, Ye N, Bao P, Zhang X, Wang F, Ma L, Chu M, Guo X, Liang C, Pan H, Yan P. Construction of transcriptome atlas of white yak hair follicle during anagen and catagen using single-cell RNA sequencing. BMC Genomics 2022; 23:813. [PMID: 36482306 PMCID: PMC9730603 DOI: 10.1186/s12864-022-09003-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 11/10/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND As the direct organ of villus, hair follicles have obvious seasonal cycles. The hair follicle cycle is orchestrated by multiple cell types that together direct cell renewal and differentiation. But the regulation property of hair follicle cells from anagen to catagen in yak is still unknown. RESULTS In this study, single-cell RNA sequencing was performed on 24,124 single cells of the scapular skin from white yak. Based on tSNE cluster analysis, the cell types of IFE-DC, epidermal cell lines, fibroblasts, keratinocytes, IRS, DS, INFU, and other cells in yak hair follicles during anagen and catagen were successfully identified, and the gene expression profiles were described. The GO enrichment analysis indicated the different cells characteristic genes to be mainly enriched in the epidermal development, epithelial cell differentiation and wound healing pathways. The pseudotime trajectory analysis described the differentiation trajectory of the epidermal lineage and dermal lineage of the hair follicle during anagen and catagen. Moreover, the dynamic changes of the genes like LHX2, KRT25, and KRT71 were found to be highly expressed in HS and IRS, but not in the IFE-DC, INFU, and keratinocyte during differentiation. CONCLUSIONS Our results analyzed the time-varying process of gene expression in the dermal cell lineage and epidermal cell lineage of hair follicles during anagen and catagen during fate differentiation was expounded at the single cell level, revealing the law of fate specialization of different types of cells. In addition, based on the enrichment analysis, the transcriptional regulatory factors involved in the different cell fates were also revealed. These results will help to enhance our understanding of yak hair follicle cycle and promote the development and utilization of yak villus.
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Affiliation(s)
- Qingbo Zheng
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Life Science and Engineering College, Northwest Minzu University, Lanzhou, 730030, China
| | - Na Ye
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Life Science and Engineering College, Northwest Minzu University, Lanzhou, 730030, China
| | - Pengjia Bao
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Xiaolan Zhang
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Fubin Wang
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Life Science and Engineering College, Northwest Minzu University, Lanzhou, 730030, China
| | - Lanhua Ma
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Life Science and Engineering College, Northwest Minzu University, Lanzhou, 730030, China
| | - Min Chu
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Xian Guo
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Chunnian Liang
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China
| | - Heping Pan
- Life Science and Engineering College, Northwest Minzu University, Lanzhou, 730030, China.
| | - Ping Yan
- Key Laboratory of Yak Breeding Engineering of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
- Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China.
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The Molecular Mechanism of Natural Products Activating Wnt/β-Catenin Signaling Pathway for Improving Hair Loss. LIFE (BASEL, SWITZERLAND) 2022; 12:life12111856. [PMID: 36430990 PMCID: PMC9693075 DOI: 10.3390/life12111856] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/28/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022]
Abstract
Hair loss, or alopecia, is a dermatological disorder that causes psychological stress and poor quality of life. Drug-based therapeutics such as finasteride and minoxidil have been clinically used to treat hair loss, but they have limitations due to their several side effects in patients. To solve this problem, there has been meaningful progress in elucidating the molecular mechanisms of hair growth and finding novel targets to develop therapeutics to treat it. Among various signaling pathways, Wnt/β-catenin plays an essential role in hair follicle development, the hair cycle, and regeneration. Thus, much research has demonstrated that various natural products worldwide promote hair growth by stimulating Wnt/β-catenin signaling. This review discusses the functional role of the Wnt/β-catenin pathway and its related signaling molecules. We also review the molecular mechanism of the natural products or compounds that activate Wnt/β-catenin signaling and provide insights into developing therapeutics or cosmeceuticals that treat hair loss.
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36
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Shin DW. The physiological and pharmacological roles of prostaglandins in hair growth. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2022; 26:405-413. [PMID: 36302616 PMCID: PMC9614392 DOI: 10.4196/kjpp.2022.26.6.405] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/07/2022]
Abstract
Hair loss is a common status found among people of all ages. Since the role of hair is much more related to culture and individual identity, hair loss can have a great influence on well-being and quality of life. It is a disorder that is observed in only scalp patients with androgenetic alopecia (AGA) or alopecia areata caused by stress or immune response abnormalities. Food and Drug Administration (FDA)-approved therapeutic medicines such as finasteride, and minoxidil improve hair loss temporarily, but when they stop, they have a limitation in that hair loss occurs again. As an alternative strategy for improving hair growth, many studies reported that there is a relationship between the expression levels of prostaglandins (PGs) and hair growth. Four major PGs such as prostaglandin D2 (PGD2), prostaglandin I2 (PGI2), prostaglandin E2 (PGE2), and prostaglandin F2 alpha (PGF2α) are spatiotemporally expressed in hair follicles and are implicated in hair loss. This review investigated the physiological roles and pharmacological interventions of the PGs in the pathogenesis of hair loss and provided these novel insights for clinical therapeutics for patients suffering from alopecia.
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Affiliation(s)
- Dong Wook Shin
- College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea,Correspondence Dong Wook Shin, E-mail:
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The Hair Growth-Promoting Effect of Gardenia florida Fruit Extract and Its Molecular Regulation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8498974. [PMID: 36193135 PMCID: PMC9526658 DOI: 10.1155/2022/8498974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 08/04/2022] [Accepted: 08/18/2022] [Indexed: 11/18/2022]
Abstract
As a herbal medicine, the extract from the fruits of Gardenia florida has been widely used for its antioxidative, hypoglycemic, and anti-inflammatory properties. However, whether G. florida fruit extract (GFFE) regulates hair growth has been rarely studied. This study was the first application of GFFE on hair growth both in vitro (human dermal papilla cells, hDPCs) and in vivo (C57BL/6 mice). The effects of GFFE on cell proliferation and hair growth-associated gene expression in hDPCs were examined. Moreover, GFFE was applied topically on the hair-shaved skin of male C57BL/6 mice, the hair length was measured, and the skin histological profile was investigated. GFFE promoted the proliferation of hDPCs and significantly stimulated hair growth-promoting genes, including vascular endothelial growth factor (VEGF) and Wnt/β-catenin signals, but suppressed the expression of the hair loss-related gene transforming growth factor-β1 (TGF-β). Furthermore, GFFE treatment resulted in a significant increase in the number, size, and depth of cultured hair follicles and stimulated the growth of hair with local effects in mice. In summary, the results provided the preclinical data to support the much potential use of the natural product GFFE as a promising agent for hair growth.
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Lef1 and Dlx3 May Facilitate the Maturation of Secondary Hair Follicles in the Skin of Gansu Alpine Merino. Genes (Basel) 2022; 13:genes13081326. [PMID: 35893063 PMCID: PMC9394301 DOI: 10.3390/genes13081326] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/20/2022] [Accepted: 07/22/2022] [Indexed: 12/04/2022] Open
Abstract
Lymphatic enhancer factor 1 (Lef1) and distal-less homeobox 3 (Dlx3) are the transcription factors involved in regulating hair follicle development in mice, goats, and other animals. Their deletion can lead to hair follicle deficiency. In this study, hematoxylin−eosin staining (HE), real-time quantitative PCR (RT-qPCR), immunohistochemistry, and immunofluorescence were used to analyze the expression, location, and biological functions of Lef1 and Dlx3 in the lateral skin of Gansu Alpine Merino aged 1, 30, 60, and 90 days. The results revealed that the number of hair follicles decreased with age and was significantly higher at 1 day than in the other three age groups (p < 0.05). The mRNA levels of Lef1 and Dlx3 in the skin of 30-day old Gansu Alpine Merino were significantly higher than those in the other three age groups (p < 0.05). Protein expression of Lef1 and Dlx3 was lowest at 1 day (p < 0.05) and peaked at 60 days. Lef1 and Dlx3 exhibited a high density and strong positive expression in the dermal papillae; additionally, Dlx3 exhibited a high density and strong positive expression in the inner and outer root sheaths. Collectively, Lef1 and Dlx3 may facilitate the maturation of secondary hair follicles, which is mainly achieved through the dermal papillae and inner and outer root sheaths.
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Wang X, Liu Y, He J, Wang J, Chen X, Yang R. Regulation of signaling pathways in hair follicle stem cells. BURNS & TRAUMA 2022; 10:tkac022. [PMID: 35795256 PMCID: PMC9250793 DOI: 10.1093/burnst/tkac022] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/07/2022] [Indexed: 11/21/2022]
Abstract
Hair follicle stem cells (HFSCs) reside in the bulge region of the outer root sheath of the hair follicle. They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity. The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions, wound repair and skin regeneration. The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways, such as lymphoid enhancer factor/T-cell factor, Wnt/β-catenin, transforming growth factor-β/bone morphogenetic protein, Notch and Hedgehog. The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied, but many mechanisms are still unclear. This article reviews the regulation of hair follicles, HFSCs and related signaling pathways, with the aims of summarizing previous research results, revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.
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Affiliation(s)
| | | | - Jia He
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China
| | - Jingru Wang
- Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China
| | - Xiaodong Chen
- Correspondence. Xiaodong Chen, E-mail: ; Ronghua Yang,
| | - Ronghua Yang
- Correspondence. Xiaodong Chen, E-mail: ; Ronghua Yang,
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Mao MQ, Jing J, Miao YJ, Lv ZF. Epithelial-Mesenchymal Interaction in Hair Regeneration and Skin Wound Healing. Front Med (Lausanne) 2022; 9:863786. [PMID: 35492363 PMCID: PMC9048199 DOI: 10.3389/fmed.2022.863786] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/16/2022] [Indexed: 11/30/2022] Open
Abstract
Interactions between epithelial and mesenchymal cells influence hair follicles (HFs) during embryonic development and skin regeneration following injury. Exchanging soluble molecules, altering key pathways, and extracellular matrix signal transduction are all part of the interplay between epithelial and mesenchymal cells. In brief, the mesenchyme contains dermal papilla cells, while the hair matrix cells and outer root sheath represent the epithelial cells. This study summarizes typical epithelial–mesenchymal signaling molecules and extracellular components under the control of follicular stem cells, aiming to broaden our current understanding of epithelial–mesenchymal interaction mechanisms in HF regeneration and skin wound healing.
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Yue Z, Li C, Liu Y, Liu M, Zhao M, Li F, Liu L. Vitamin A alleviates heat stress-induced damage to hair follicle development in Rex rabbits. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2022; 102:2291-2299. [PMID: 34625979 DOI: 10.1002/jsfa.11567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 10/09/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Rex rabbits are important fur rabbits. Heat stress severely reduces the fur quality of Rex rabbits. The aim of this study was to experimentally investigate the effect of dietary vitamin A (VA) addition on hair follicle development and related signal pathways in Rex rabbits under heat stress. RESULTS In the experiment, 90 Rex rabbits were randomly divided into three groups: control group (20-25 °C, fed basic diet), heat stress group (30-34 °C, fed basic diet), and heat stress + VA group (20-25 °C, fed 12 000 IU/kg VA in addition to the basic diet). VA could significantly increase the hair follicle density (P < 0.01), hair length (P < 0.05), and the ratio of secondary to primary hair follicles (P < 0.05). In addition, VA could significantly inhibit the expression of BMP2, BMP4, FGF5, TGF-β1, and miR-214 in heat-stressed Rex rabbits and significantly increase the expression of noggin, IGF1, IGF1R, Wnt10b, CTNNB1, SHH, and miR-203 and the levels of Wnt10b and p-β-catenin; however, there was no significant effect of VA on the expression of EGF and miR-205. CONCLUSION The dietary addition of VA can increase the hair follicle density and fur quality of heat-stressed Rex rabbits. Wnt10/β-catenin, insulin-like growth factor 1 (IGF1), fibroblast growth factor 5 (FGF5), noggin-BMP, and sonic hedgehog (SHH) signaling were associated with VA regulation under heat stress. It is possible that miR-205 and miR-194 contribute to the regulation of Wnt10/β-catenin and bone morphogenetic protein (BMP) signaling. © 2021 Society of Chemical Industry.
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Affiliation(s)
- Zhengkai Yue
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
| | - Chenyang Li
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
| | - Yongxu Liu
- Qingdao Kangda Food Co., Ltd., Qingdao, China
| | - Mengqi Liu
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
| | - Man Zhao
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
| | - Fuchang Li
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
| | - Lei Liu
- Department of Animal Science, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, China
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Kim H, Jang Y, Kim EH, Jang H, Cho H, Han G, Song HK, Kim SH, Yang Y. Potential of Colostrum-Derived Exosomes for Promoting Hair Regeneration Through the Transition From Telogen to Anagen Phase. Front Cell Dev Biol 2022; 10:815205. [PMID: 35359449 PMCID: PMC8960251 DOI: 10.3389/fcell.2022.815205] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 02/22/2022] [Indexed: 12/18/2022] Open
Abstract
Human hair dermal papillary (DP) cells comprising mesenchymal stem cells in hair follicles contribute critically to hair growth and cycle regulation. The transition of hair follicles from telogen to anagen phase is the key to regulating hair growth, which relies heavily on the activation of DP cells. In this paper, we suggested exosomes derived from bovine colostrum (milk exosomes, Milk-exo) as a new effective non-surgical therapy for hair loss. Results showed that Milk-exo promoted the proliferation of hair DP cells and rescued dihydrotestosterone (DHT, androgen hormones)-induced arrest of follicle development. Milk-exo also induced dorsal hair re-growth in mice at the level comparable to minoxidil treatment, without associated adverse effects such as skin rashes. Our data demonstrated that Milk-exo accelerated the hair cycle transition from telogen to anagen phase by activating the Wnt/β-catenin pathway. Interestingly, Milk-exo has been found to stably retain its original properties and efficacy for hair regeneration after freeze-drying and resuspension, which is considered critical to use it as a raw material applied in different types of alopecia medicines and treatments. Overall, this study highlights a great potential of an exosome from colostrum as a therapeutic modality for hair loss.
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Affiliation(s)
- Hyosuk Kim
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
| | - Yeongji Jang
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- Department of Life Science, Korea University, Seoul, South Korea
| | - Eun Hye Kim
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- Department of Life Science, Korea University, Seoul, South Korea
| | - Hochung Jang
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- Division of Bio‐Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
| | - Haeun Cho
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- Department of Biotechnology, Korea University, Seoul, South Korea
| | - Geonhee Han
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, South Korea
| | - Hyun Kyu Song
- Department of Life Science, Korea University, Seoul, South Korea
| | - Sun Hwa Kim
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- *Correspondence: Sun Hwa Kim, ; Yoosoo Yang,
| | - Yoosoo Yang
- Center for Theragnosis, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, South Korea
- Division of Bio‐Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
- *Correspondence: Sun Hwa Kim, ; Yoosoo Yang,
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Neri TAN, Palmos GN, Park SY, Jung TS, Choi BD. Hair Growth-Promoting Activities of Glycosaminoglycans Extracted from the Tunics of Ascidian ( Halocynthia roretzi). Polymers (Basel) 2022; 14:polym14061096. [PMID: 35335427 PMCID: PMC8950973 DOI: 10.3390/polym14061096] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/21/2022] [Accepted: 02/28/2022] [Indexed: 02/01/2023] Open
Abstract
Throughout the ages, hair has had psychological and sociological importance in framing the personality and general appearance of an individual. Despite efforts to solve this problem, no groundbreaking measures have been proposed. Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Three fractions (F1, F2 and F3) were obtained after separation and purification of GAGs from ascidian tunics. F1 was observed to contain a small amount of amino sugar while high contents of galactose and N-acetylglucosamine were noted in F2 and F3. 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (∆Di-6S) and 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (∆Di-4S) were the main disaccharide components. F3 exhibited the highest proliferation activity on human follicle dermal papilla (HFDP) cells. In addition, mixed samples (FFM) of F2 and F3 at different concentrations showed peak activities for five days. After cell culture at a concentration of 10 mg/mL and dihydrotestosterone (DHT), the inhibition effect was higher than that for Minoxidil. Application of 10 mg of FFM to the hair of mice for 28 days resulted in a hair growth effect similar to that of Minoxidil, a positive control.
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Affiliation(s)
- Therese Ariane N. Neri
- Nutrition Chemistry Laboratory, Department of Seafood Science and Technology, The Institute of Marine Industry, Gyeongsang National University, Tongyeong 53064, Korea;
| | - Grace N. Palmos
- Institute of Fish Processing Technology, College of Fisheries and Ocean Sciences, University of the Philippines Visayas, Iloilo 5023, Philippines;
| | - Shin Young Park
- Food Hygiene Laboratory, Department of Seafood Science and Technology, The Institute of Marine Industry, Gyeongsang National University, Tongyeong 53064, Korea;
| | - Tae Sung Jung
- Laboratory of Aquatic Animal Diseases, Research Institute of Natural Science, College of Veterinary Medicine, Gyeongsang National University, Jinju-daero, Jinju 52828, Korea;
| | - Byeong-Dae Choi
- Nutrition Chemistry Laboratory, Department of Seafood Science and Technology, The Institute of Marine Industry, Gyeongsang National University, Tongyeong 53064, Korea;
- Correspondence: ; Tel.: +82-55-772-9142; Fax: +82-55-772-9149
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Mokabber H, Vatankhah MA, Najafzadeh N. The regulatory role of microRNAs in the development, cyclic changes, and cell differentiation of the hair follicle. Process Biochem 2022; 114:36-41. [DOI: 10.1016/j.procbio.2022.01.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Exosomes Secreted from Adipose-Derived Stem Cells Are a Potential Treatment Agent for Immune-Mediated Alopecia. J Immunol Res 2022; 2022:7471246. [PMID: 35155688 PMCID: PMC8831060 DOI: 10.1155/2022/7471246] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 12/29/2021] [Accepted: 01/08/2022] [Indexed: 12/19/2022] Open
Abstract
Background Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. Methods Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real‐time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). Results ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/β-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. Conclusion ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/β-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.
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Yuen GKW, Ho BSY, Lin LSY, Dong TTX, Tsim KWK. Tectoridin Stimulates the Activity of Human Dermal Papilla Cells and Promotes Hair Shaft Elongation in Mouse Vibrissae Hair Follicle Culture. Molecules 2022; 27:400. [PMID: 35056713 PMCID: PMC8778330 DOI: 10.3390/molecules27020400] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 01/04/2022] [Accepted: 01/05/2022] [Indexed: 02/01/2023] Open
Abstract
To search hair growth-promoting herbal extract, a screening platform of having HEK293T fibroblast being transfected with pTOPFLASH DNA construct was developed over a thousand of herbal extracts and phytochemicals were screened. One of the hits was ethanolic extract of Rhizoma Belamcandae, the rhizome of Belamcanda chinensis (L.) DC. Tectoridin, an isoflavone from Rhizoma Belamcandae, was shown to be responsible for this activation of promoter construct, inducing the transcription of pTOPFLASH in the transfected fibroblasts in a dose-dependent manner. The blockage by DKK-1 suggested the action of tectoridin could be mediated by the Wnt receptor. The hair growth-promoting effects of tectoridin were illustrated in human follicular dermal papilla cells and mouse vibrissae organ cultures. In tectoridin-treated dermal papilla cultures, an activation of Wnt signaling was demonstrated by various indicative markers, including TCF/LEF1 transcriptional activity, nuclear translocation of β-catenin, expressions level of mRNAs encoding axin-related protein, (AXIN2), β-catenin, lymphoid enhancer-binding factor-1 (LEF-1), insulin-like growth factor 1 (IGF-1) and alkaline phosphatase (ALP). In addition, an increase of hair shaft elongation was observed in cultured mouse vibrissae upon the treatment of tectoridin. Tectoridin, as well as the herbal extract of Rhizoma Belamcandae, possesses hair promoting activity, which deserves further development.
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Affiliation(s)
- Gary Ka-Wing Yuen
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen 518057, China; (G.K.-W.Y.); (T.T.-X.D.)
- Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; (B.S.-Y.H.); (L.S.-Y.L.)
| | - Bryan Siu-Yin Ho
- Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; (B.S.-Y.H.); (L.S.-Y.L.)
| | - Lish Sheng-Ying Lin
- Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; (B.S.-Y.H.); (L.S.-Y.L.)
| | - Tina Ting-Xia Dong
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen 518057, China; (G.K.-W.Y.); (T.T.-X.D.)
- Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; (B.S.-Y.H.); (L.S.-Y.L.)
| | - Karl Wah-Keung Tsim
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen 518057, China; (G.K.-W.Y.); (T.T.-X.D.)
- Division of Life Science and Centre for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; (B.S.-Y.H.); (L.S.-Y.L.)
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Painter KJ, Ptashnyk M, Headon DJ. Systems for intricate patterning of the vertebrate anatomy. PHILOSOPHICAL TRANSACTIONS. SERIES A, MATHEMATICAL, PHYSICAL, AND ENGINEERING SCIENCES 2021; 379:20200270. [PMID: 34743605 PMCID: PMC8580425 DOI: 10.1098/rsta.2020.0270] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/11/2021] [Indexed: 05/05/2023]
Abstract
Periodic patterns form intricate arrays in the vertebrate anatomy, notably the hair and feather follicles of the skin, but also internally the villi of the gut and the many branches of the lung, kidney, mammary and salivary glands. These tissues are composite structures, being composed of adjoined epithelium and mesenchyme, and the patterns that arise within them require interaction between these two tissue layers. In embryonic development, cells change both their distribution and state in a periodic manner, defining the size and relative positions of these specialized structures. Their placement is determined by simple spacing mechanisms, with substantial evidence pointing to a variety of local enhancement/lateral inhibition systems underlying the breaking of symmetry. The nature of the cellular processes involved, however, has been less clear. While much attention has focused on intercellular soluble signals, such as protein growth factors, experimental evidence has grown for contributions of cell movement or mechanical forces to symmetry breaking. In the mesenchyme, unlike the epithelium, cells may move freely and can self-organize into aggregates by chemotaxis, or through generation and response to mechanical strain on their surrounding matrix. Different modes of self-organization may coexist, either coordinated into a single system or with hierarchical relationships. Consideration of a broad range of distinct biological processes is required to advance understanding of biological pattern formation. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.
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Affiliation(s)
- Kevin J. Painter
- Dipartimento Interateneo di Scienze, Progetto e Politiche del Territorio, Politecnico di Torino, Torino, Italy
| | - Mariya Ptashnyk
- School of Mathematical and Computer Sciences and Maxwell Institute, Heriot-Watt University, Edinburgh, UK
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Zhang X, Lei T, Chen P, Wang L, Wang J, Wang D, Guo W, Zhou Y, Li Q, Du H. Stem Cells from Human Exfoliated Deciduous teeth Promote Hair Regeneration in Mouse. Cell Transplant 2021; 30:9636897211042927. [PMID: 34633878 PMCID: PMC8512255 DOI: 10.1177/09636897211042927] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Stem cells in different types may interact with each other to maintain
homeostasis or growth and the interactions are complicated and extensive. There
is increasing evidence that mesenchymal-epithelial interactions in early
morphogenesis stages of both tooth and hair follicles show many similarities. In
order to explore whether stem cells from one tissue could interact with cells
from another tissue, a series of experiments were carried out. Here we
successfully extracted and identified stem cells from human exfoliated deciduous
teeth (SHED) of 8–12 years old kids, and then found that SHED could promote hair
regeneration in a mouse model. In vitro, SHED shortened the hair regeneration
cycle and promoted the proliferation and aggregation of dermal cells. In vivo,
when SHED and skin cells of C57 mice were subcutaneously co-transplanted to nude
mice, more hair was formed than skin cells without SHED. To further explore the
molecular mechanism, epidermal and dermal cells were freshly extracted and
co-cultured with SHED. Then several signaling molecules in hair follicle
regeneration were detected and we found that the expression of Sonic Hedgehog
(Shh) and Glioma-associated oncogene 1 (Gli1) was up-regulated. It seems that
SHED may boost the prosperity of hairs by increase Shh/Gli1 pathway, which
brings new perspectives in tissue engineering and damaged tissue repairing.
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Affiliation(s)
- Xiaoshuang Zhang
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Tong Lei
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Peng Chen
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing, China
| | - Lei Wang
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China
| | - Jian Wang
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China
| | - Donghui Wang
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Wenhuan Guo
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Yabin Zhou
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
| | - Quanhai Li
- Cell Therapy Laboratory, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.,Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, China
| | - Hongwu Du
- Daxing Research Institute, University of Science and Technology Beijing, Beijing, China.,School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
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49
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Shi X, Jiang N, Mao J, Luo D, Liu Y. Mesenchymal stem cell‐derived exosomes for organ development and cell‐free therapy. NANO SELECT 2021. [DOI: 10.1002/nano.202000286] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Xin Shi
- Center and School of Stomatology Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan P.R. China
- Laboratory of Biomimetic Nanomaterials Department of Orthodontics National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing P.R. China
| | - Nan Jiang
- Laboratory of Biomimetic Nanomaterials Department of Orthodontics National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing P.R. China
- Central Laboratory National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing P.R. China
| | - Jing Mao
- Center and School of Stomatology Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan P.R. China
| | - Dan Luo
- CAS Center for Excellence in Nanoscience Beijing Key Laboratory of Micro‐nano Energy and Sensor Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing P.R. China
| | - Yan Liu
- Laboratory of Biomimetic Nanomaterials Department of Orthodontics National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology Peking University School and Hospital of Stomatology Beijing P.R. China
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50
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Aamar E, Laron EA, Asaad W, Harshuk-Shabso S, Enshell-Seijffers D. Hair-follicle mesenchymal stem-cell activity during homeostasis and wound healing. J Invest Dermatol 2021; 141:2797-2807.e6. [PMID: 34166673 DOI: 10.1016/j.jid.2021.05.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 05/10/2021] [Accepted: 05/11/2021] [Indexed: 10/21/2022]
Abstract
The mesenchymal components of the hair follicle, the dermal papilla (DP) and dermal sheath (DS), are maintained by hair-follicle dermal stem cells (hfDSCs), but the position of this stem cell population throughout the hair cycle, its contribution to the maintenance of the dermis and the existence of a migratory axis from the DP to the dermis remain unclear. Here we show that during homeostasis DP and DS cells are confined to their compartments, and during the regression phase of the hair cycle, some undergo apoptosis and subsequently are internalized by nearby adipocytes. In contrast, during wound healing, DP/DS cells move towards the wound, but do not directly participate in follicle neogenesis. Furthermore, hfDSCs, driving the cyclic renewal of the DS during the hair cycle, are heterogeneous and housed during the growth phase within the most proximal part of the DS. Our analysis provides insight into the mechanisms of tissue maintenance and unravels a previously-unknown potential function of adipocytes in phagocytosis.
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Affiliation(s)
- Emil Aamar
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Efrat Avigad Laron
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Wisal Asaad
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Sarina Harshuk-Shabso
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - David Enshell-Seijffers
- The Laboratory of Developmental Biology, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
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