• Adipose stromal cells
• Comparative analysis
• Mesenchymal stromal cells
• Preconditioning
• Proteomics

• Humans
• Secretome
• Mesenchymal Stem Cells/metabolism
• Adipocytes/metabolism
• Cytokines/metabolism
• Hypoxia
• Reference Standards

• Knee
• Osteoarthritis
• Prognostic factors
• Stromal vascular fraction

• COVID-19
• Innate immunity
• Oncogenesis
• PTX3
• Tissue remodeling

• Humans
• Endothelial Cells/metabolism
• C-Reactive Protein/genetics
• C-Reactive Protein/metabolism
• Inflammation/metabolism
• Immunity, Innate
• Carcinogenesis
• COVID-19 Drug Treatment

Obesity is characterized as a disease that directly affects the whole-body metabolism and is associated with excess fat mass and several related comorbidities. Dynamics of adipocyte hypertrophy and hyperplasia play an important role in health and disease, especially in obesity. Human adipose-derived stem cells (hASC) represent an important source for understanding the entire adipogenic differentiation process. However, little is known about the triggering step of adipogenesis in hASC. Here, we performed a proteogenomic approach for understanding the protein abundance alterations during the initiation of the adipogenic differentiation process.

hASC were isolated from adipose tissue of three donors and were then characterized and expanded. Cells were cultured for 24 hours in adipogenic differentiation medium followed by protein extraction. We used shotgun proteomics to compare the proteomic profile of 24 h-adipogenic, differentiated, and undifferentiated hASC. We also used our previous next-generation sequencing data (RNA-seq) of the total and polysomal mRNA fractions of hASC to study posttranscriptional regulation during the initial steps of adipogenesis.

We identified 3420 proteins out of 48,336 peptides, of which 92 proteins were exclusively identified in undifferentiated hASC and 53 proteins were exclusively found in 24 h-differentiated cells. Using a stringent criterion, we identified 33 differentially abundant proteins when comparing 24 h-differentiated and undifferentiated hASC (14 upregulated and 19 downregulated, respectively). Among the upregulated proteins, we shortlisted several adipogenesis-related proteins. A combined analysis of the proteome and the transcriptome allowed the identification of positive correlation coefficients between proteins and mRNAs.

These results demonstrate a specific proteome profile related to adipogenesis at the beginning (24 hours) of the differentiation process in hASC, which advances the understanding of human adipogenesis and obesity. Adipogenic differentiation is finely regulated at the transcriptional, posttranscriptional, and posttranslational levels.

• distal-less homeobox 5
• peroxisome proliferator-activated receptor γ
• transcription

• PAI-1
• PAS
• adipocytes
• uPA

• Exosomes
• Mesenchymal stem cells
• Oxidative stress
• Regenerative medicine
• Secretome

Naturally-derived proteins or peptides are promising biopolymers for tissue engineering applications owing to their health-promoting activity. Herein, we extracted proteins (~90%) from two-spotted cricket (Gryllus bimaculatus) and evaluated their osteoinductive potential in human bone marrow-derived mesenchymal stem cells (hBMSCs) under in vitro conditions. The extracted protein isolate was analyzed for the amino acid composition and the mass distribution of the constituent peptide fraction. Fourier transform infrared (FTIR) spectroscopy was used to determine the presence of biologically significant functional groups. The cricket protein isolate (CPI) exhibited characteristic protein peaks in the FTIR spectrum. Notably, an enhanced cell viability was observed in the presence of the extracted proteins, showing their biocompatibility. The CPI also exhibited antioxidant properties in a concentration-dependent manner. More significant mineralization was observed in the CPI-treated cells than in the control, suggesting their osteoinductive potential. The upregulation of the osteogenic marker genes (Runx2, ALP, OCN, and BSP) in CPI treated media compared with the control supports their osteoinductive nature. Therefore, cricket-derived protein isolates could be used as functional protein isolate for tissue engineering applications, especially for bone regeneration.

• Animals
• Antioxidants/metabolism
• Cell Differentiation
• Cells, Cultured
• Gryllidae
• Humans
• Insect Proteins/administration & dosage
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/drug effects
• Mesenchymal Stem Cells/metabolism
• Osteogenesis
• Tissue Engineering
• Tissue Extracts/pharmacology

• 'National Research Foundation of Korea
• National Research Foundation of Korea
• Innovative Cultured Meat Technology Development Alchemist Project

• biomaterials
• cells
• chronic limb threatening ischemia
• growth factors
• nucleic acids

• Biocompatible Materials/therapeutic use
• Chronic Disease
• Humans
• Ischemia/physiopathology
• Ischemia/therapy
• Limb Salvage
• Lower Extremity/blood supply
• Peripheral Arterial Disease/physiopathology
• Peripheral Arterial Disease/therapy

• Science Foundation Ireland
• European Regional Development Fund
• National University of Ireland

• adipose tissue derived stem cells
• extracellular vesicles
• mesenchymal
• micro vesicles
• paracrine effect
• radiation
• stem cell

• adipogenesis
• long noncoding RNA
• mesenchymal stem cell
• tissue engineering

• 81971518 the National Natural Science Foundation of China
• 19ykpy01 the Fundamental Research Fundus for the Central Universities of China
• ZDSYS20190902092851024 the Shenzhen Key Medical Discipline Construction Fund
• FTWS2019020 the Health Welfare Fund Project of Futian District

• Q-graft®
• adipose tissue-derived stem/stromal cells (ASCs)
• osteoarthritis (OA)
• stromal vascular fraction (SVF)
• therapeutics

• Adipose Tissue/cytology
• Adipose Tissue/surgery
• Aged
• Aged, 80 and over
• Female
• Follow-Up Studies
• Humans
• Injections, Intra-Articular
• Knee Joint/diagnostic imaging
• Knee Joint/pathology
• Magnetic Resonance Imaging
• Male
• Mesenchymal Stem Cell Transplantation/methods
• Middle Aged
• Osteoarthritis, Knee/diagnostic imaging
• Osteoarthritis, Knee/pathology
• Osteoarthritis, Knee/therapy
• Patient Satisfaction
• Platelet-Rich Plasma
• Treatment Outcome

Osteoarthritis (OA) is a common joint disorder with a significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose tissue has recently been highlighted as a major contributor to OA through strong inflammation mediating effects. In this study, methacrylated gelatin (GelMA) constructs seeded with adipose tissue-derived mesenchymal stem cells (ASCs) and cultured in a 3D printed bioreactor were investigated for use in microphysiological systems to model adipose tissue in the knee joint. Four patient-derived ASC populations were seeded at a density of 20 million cells/mL in GelMA. Live/Dead and boron-dipyrromethene/4′,6-diamidino-2-phenylindole (BODIPY/DAPI) staining of cells within the constructs demonstrated robust cell viability after 28 days in a growth (control) medium, and robust cell viability and lipid accumulation in adipogenic differentiation medium. qPCR gene expression analysis and protein analysis demonstrated an upregulated expression of key adipogenesis-associated genes. Overall, these data indicate that ASCs retain their adipogenic potential when seeded within GelMA hydrogels and cultured within perfusion bioreactors, and thus can be used in a 3D organ-on-a-chip system to study the role of the IPFP in the pathobiology of the knee OA.

• adipocytes
• adipose stem cells
• methacrylated gelatin
• microphysiological system
• osteoarthritis
• tissue-on-a-chip

The innate immune system is equipped with a number of germ-line encoded soluble pattern recognition molecules (PRMs) that collectively mediate the humoral host response to infection and damage in cooperation with cells and tissues of the immune and non-immune compartments. Despite the impressive diversity in structure, source, and regulation across PRMs, these all share remarkably similar functions inasmuch as they recognize microbes and damaged tissues, activate complement, exert opsono-phagocytic activities, and regulate inflammation. The long pentraxin 3 (PTX3) is a prototypic soluble PRM. Long known as a major player in innate immunity, inflammation and matrix remodeling, only recently has PTX3 emerged as a mediator of bone homeostasis in rodents and humans. Ptx3-targeted mice exhibit reduced trabecular volume during bone development, and impaired callus mineralization following experimental fracture. The murine gene is expressed in vivo by non-hematopoietic periosteal cells in the early phases of fracture healing, and in vitro by maturing osteoblasts. Human osteoblasts do express the PTX3 protein, whose levels positively correlate with bone density in vivo and osteoblast proliferation and maturation in vitro, thus pointing to a role in bone deposition. Contrasting evidence, however, suggest osteoclastogenesis-promoting effects of PTX3, where its expression has been associated with periodontitis, arthritis, and bone metastasis, conditions hallmarked by inflammation and bone resorption. Here, we review past and recent literature on the functions exerted by this long pentraxin in bone biology, with major emphasis on physiological skeletal remodeling, fracture healing, and chronic diseases of the bone.

• PTX3
• osteoblasts
• osteoimmunology
• pentraxins
• periodontitis

• bioreactors
• mass spectrometry
• mesenchymal stem/stromal cells
• proteomic analysis
• secretome
• umbilical cord matrix

• ACTN1
• LRP1
• LTBP4
• adipogenesis from hMSCs
• alternative splicing events

Diabetes mellitus (DM) is well-known to exert complications such as retinopathy, cardiomyopathy and neuropathy. However, in recent years, an elevated osteoarthritis (OA) complaints among diabetics have been observed, portending the risk of diabetic OA. Since formation of advanced glycation end products (AGE) is believed to be the etiology of various diseases under hyperglycemic conditions, we firstly established that streptozotocin-induced DM could potentiate the development of OA in C57BL/6J mouse model, and further explored the intra-articularly administered adipose-derived stem cell (ADSC) therapy focusing on underlying AGE-associated mechanism. Our results demonstrated that hyperglycemic mice exhibited OA-like structural impairments including a proteoglycan loss and articular cartilage fibrillations in knee joint. Highly expressed levels of carboxymethyl lysine (CML), an AGE and their receptors (RAGE), which are hallmarks of hyperglycemic microenvironment were manifested. The elevated oxidative stress in diabetic OA knee-joint was revealed through increased levels of malondialdehyde (MDA). Further, oxidative stress-activated nuclear factor kappa B (NF-κB), the marker of proinflammatory signalling pathway was also accrued; and levels of matrix metalloproteinase-1 and 13 were upregulated. However, ADSC treatment attenuated all OA-like changes by 4 weeks, and dampened levels of CML, RAGE, MDA, NF-κB, MMP-1 and 13. These results suggest that during repair and regeneration, ADSCs inhibited glycation-mediated inflammatory cascade and rejuvenated cartilaginous tissue, thereby promoting knee-joint integrity in diabetic milieu.

• Diabetes mellitus
• adipose-derived stem cells
• advanced glycation end product
• articular cartilage
• osteoarthritis
• proteoglycans

• Neurodegeneration
• neurons
• secretome
• stem cells
• stress granules

• Animals
• Arsenites
• Astrocytes/metabolism
• Caspase 3/metabolism
• Caspase 7/metabolism
• Cells, Cultured
• Culture Media, Conditioned/pharmacology
• Exosomes/metabolism
• Fibroblasts/metabolism
• Glutamic Acid
• Humans
• L-Lactate Dehydrogenase/metabolism
• Mesenchymal Stem Cells/metabolism
• Nerve Degeneration/pathology
• Nerve Degeneration/physiopathology
• Nerve Regeneration/drug effects
• Neural Stem Cells/metabolism
• Neurites/drug effects
• Neurites/physiology
• Oxidative Stress/drug effects
• Oxidative Stress/physiology
• Rats
• Stem Cells/metabolism

• bone biomechanics
• metabolism
• osteoporosis
• parathyroid hormone
• transcriptome

• Animals
• Bone Matrix/metabolism
• Calcification, Physiologic/genetics
• Collagen/genetics
• Collagen/metabolism
• Gene Expression Profiling
• Gene Expression Regulation
• Glycolysis/genetics
• Mesenchymal Stem Cells/metabolism
• Mice
• Mice, Knockout
• Nuclear Matrix-Associated Proteins/genetics
• Osteoblasts/cytology
• Osteoblasts/metabolism
• Osteogenesis/genetics
• Osteoporosis/metabolism
• RNA, Messenger/metabolism
• Transcription Factors/genetics

• R01 GM049164 NIGMS NIH HHS
• K25 AR067221 NIAMS NIH HHS
• P30 DK097512 NIDDK NIH HHS
• R01 NS098772 NINDS NIH HHS
• R01 AR073739 NIAMS NIH HHS

• Brain
• Mesenchymal stem cells
• Paracrine factors
• Pathologies
• Secretome
• Therapeutics

This research aimed to investigate the relationship between abdominal obesity and lower bone mineral density (BMD) at non-weight-bearing site in Korean men using data from the Korea National Health and Nutrition Examination Survey, which is a nationwide cross-sectional survey. The study population (n = 5,941) was selected from the 2009–2010 survey. Abdominal obesity in men was defined as waist circumference ⩾ 90 cm. Lower BMD state was defined as having T-score of −2.5 or below. To investigate the association, multiple logistic regression analysis was performed. Abdominal obesity was highly associated with lower non-weight-bearing site (lumbar spine [LS]) BMD after adjustment (odds ratio [OR] 1.61, 95% CI [1.06, 2.44], p = .026). Also, abdominal obesity was a risk factor for lower LS BMD, especially in age groups of those in their 20s and those over 60s (OR 5.53, 95% CI [1.27, 24.07], p = .023 for 20s; OR 2.19, 95% CI [1.19, 4.02], p = .011 for 60 years or older). Abdominal obesity in Korean men is associated with lower BMD at non-weight-bearing site (LS), especially in younger and older age groups. Further research might be recommended to prove the mechanism or causality.

• Korean men
• abdominal obesity
• bone mineral density
• non-weight-bearing site

• cell niches
• plasminogen activator inhibitors
• regeneration
• stem cells
• urokinase
• urokinase receptor

• characterization
• expansion
• harvesting
• human adipose-derived stem cells
• isolation

• Diabetes
• Obesity
• Selenium
• Thioredoxin interacting protein
• Thioredoxin reductase

• Adipose Tissue/metabolism
• Adipose Tissue/physiopathology
• Animals
• Atherosclerosis/diagnosis
• Atherosclerosis/metabolism
• Atherosclerosis/physiopathology
• Atherosclerosis/therapy
• Diabetes Mellitus/diagnosis
• Diabetes Mellitus/metabolism
• Diabetes Mellitus/physiopathology
• Diabetes Mellitus/therapy
• Humans
• Hypertension/diagnosis
• Hypertension/metabolism
• Hypertension/physiopathology
• Hypertension/therapy
• Metabolic Syndrome/diagnosis
• Metabolic Syndrome/metabolism
• Metabolic Syndrome/physiopathology
• Metabolic Syndrome/therapy
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/physiopathology
• Non-alcoholic Fatty Liver Disease/therapy
• Obesity/diagnosis
• Obesity/metabolism
• Obesity/physiopathology
• Obesity/therapy
• Prognosis
• Thioredoxin-Disulfide Reductase/metabolism
• Thioredoxins/metabolism

• Ministry of Education and Science of the Russian Federation

Adipose tissue secretes a plethora of adipokines as evidenced by characterization of subcutaneous and visceral adipose tissue secretomes. However, adipose tissue composition and secretion pattern is depot and disease dependent, influencing the adipose tissue secretome. We investigated the secretome of cancer-associated adipose tissue (CAAT) explants from breast cancer patients and explored its role in breast cancer proliferation. CAAT proteins were identified by LC-MS/MS and human protein antibody arrays and stimulated proliferation of three breast cancer cell lines. Kinomics and transcriptomics of MCF-7 breast cancer cells treated with the secretome of CAAT revealed activation of Akt-, ERK- and JNK-pathways and differential expression of activator protein 1 (AP-1) and cAMP responsive element-binding protein (CREB) target genes. The cyclin-dependent kinase (CDK)4/6-inhibitor palbociclib significantly abrogated CAAT-enhanced breast cancer cell proliferation. Our work characterizes the specific breast CAAT protein secretome and reveals its pro-proliferative potency in breast cancer.

• adipose tissue
• breast cancer
• palbociclib
• proliferation
• secretome

• Adipose Tissue/cytology
• Adipose Tissue/metabolism
• Cells, Cultured
• Cellular Senescence
• Humans
• Insulin-Like Growth Factor Binding Proteins/metabolism
• Lamin Type A/metabolism
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Osteogenesis
• Proteome/analysis

Pentraxin 3 (PTX3) is an inflammatory mediator acting as a fluid-phase pattern recognition molecule and playing an essential role in innate immunity and matrix remodeling. Inflammatory mediators also contribute to skeletal homeostasis, operating at multiple levels in physiological and pathological conditions. This study was designed to investigate the role of PTX3 in physiological skeletal remodeling and bone healing. Micro-computed tomography (μCT) and bone histomorphometry of distal femur showed that PTX3 gene-targeted female and male mice (ptx3^−/−) had lower trabecular bone volume than their wild-type (ptx3^+/+) littermates (BV/TV by μCT: 3.50 ± 1.31 vs 6.09 ± 1.17 for females, p < 0.0001; BV/TV 9.06 ± 1.89 vs 10.47 ± 1.97 for males, p = 0.0435). In addition, μCT revealed lower trabecular bone volume in second lumbar vertebra of ptx3^−/− mice. PTX3 was increasingly expressed during osteoblast maturation in vitro and was able to reverse the negative effect of fibroblast growth factor 2 (FGF2) on osteoblast differentiation. This effect was specific for the N-terminal domain of PTX3 that contains the FGF2-binding site. By using the closed transversal tibial fracture model, we found that ptx3^−/− female mice formed significantly less mineralized callus during the anabolic phase following fracture injury compared to ptx3^+/+ mice (BV/TV 17.05 ± 4.59 vs 20.47 ± 3.32, p = 0.0195). Non-hematopoietic periosteal cells highly upregulated PTX3 expression during the initial phase of fracture healing, particularly CD51⁺ and αSma⁺ osteoprogenitor subsets, and callus tissue exhibited concomitant expression of PTX3 and FGF2 around the fracture site. Thus, PTX3 supports maintenance of the bone mass possibly by inhibiting FGF2 and its negative impact on bone formation. Moreover, PTX3 enables timely occurring sequence of callus mineralization after bone fracture injury. These results indicate that PTX3 plays an important role in bone homeostasis and in proper matrix mineralization during fracture repair, a reflection of the function of this molecule in tissue homeostasis and repair.

• bone healing
• bone turnover
• fibroblast growth factor 2
• inflammation
• osteoblast
• osteoclast
• pentraxin 3

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prion-like disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.

• Amyotrophic lateral sclerosis
• Proteins
• Stem cells
• Extracellular matrix
• Exposome
• Heat shock protein
• Stem cell molecules

Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.

• clinical trial
• exosomes
• mitochondria
• secretome
• stem cell therapy
• “cell free” therapy

Maintenance of the adipose tissue requires a proper balance between self-renewal and differentiation of adipose progenitors (AP). Any deregulation leads either to fat overexpansion and obesity or fat loss and consequent lipodystrophies. Depending on the fat pad location, APs and adipocytes are heterogeneous. However, information on the pharmacological sensitivity of distinct APs to drugs known to alter the function of adipose tissue, especially HIV protease inhibitors (PIs) is scant. Here we show that PIs decreased proliferation and clonal expansion of APs, modifying their self-renewal potential. Lopinavir was the most potent PI tested. Decrease in self-renewal was accompanied by a reduced expression of the immediate early response gene IER3, a gene associated with tissue expansion. It was more pronounced in chin-derived APs than in knee-derived APs. Furthermore, lopinavir lowered the activin A–induced ERK1/2 phosphorylation. Expressions of the transcription factor EGR1 and its targets, including INHBA were subsequently altered. Therefore, activin A secretion was reduced leading to a dramatic impairment of APs self-renewal sustained by the activin A autocrine loop. All together, these observations highlight the activin A autocrine loop as a crucial effector to maintain APs self-renewal. Targeting this pathway by HIV-PIs may participate in the induction of unwanted side effects.

Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3.

We conducted a prospective experimental interventional study on wild-type (WT) and PTX3-deficient (PTX3^−/−) mice. Acute lung injury was induced in WT and PTX3^−/− mice by instillation of hydrochloric acid into the right bronchus. One hour later, animals received intraperitoneal sterile phosphate-buffered saline (PBS), WT-MSCs (1 × 10⁶) or PTX3^−/−-MSCs (1 × 10⁶). Twenty-four hours after injury, we measured the effects of treatments on arterial blood gases, wet/dry lung weight (W/D), CT scan analysis of lung collapse, neutrophils, TNFα and CXCL1 in bronchoalveolar lavage, and plasma PTX3. d-dimer was assayed in 1 week and OH-proline in 2 weeks to track the fibrotic evolution.

In 24 h, in comparison to PBS, WT-MSCs improved oxygenation and reduced W/D and alveolar collapse. These effects were associated with decreased concentrations of alveolar neutrophils and cytokines. WT-MSCs increased d-dimer concentration and decreased OH-proline levels, too.

Treatment with PTX3^−/−-MSCs ameliorated oxygenation, W/D, and alveolar TNFα, though to a lesser extent than WT-MSCs. PTX3^−/−-MSCs did not improve lung collapse, neutrophil count, CXCL1, d-dimer, and OH-proline concentrations. The protective effects of WT-MSCs were dampened by lack of endogenous PTX3, too.

In acid aspiration acute lung injury, MSCs improve pulmonary function and limit fibrosis by fine-tuning inflammation. The role of PTX3 in determining MSCs’ effects might merit further scrutiny.

The online version of this article (doi:10.1186/s40635-017-0126-5) contains supplementary material, which is available to authorized users.

• Acid aspiration syndrome
• Acute lung injury
• Acute respiratory distress syndrome
• Pentraxin 3
• Stem cells

• Adipocyte differentiation
• Antagonist
• GGPP
• LXR
• Metabolic syndrome

• cell-based therapeutics
• mesenchymal stromal cells
• platelet lysate
• preclinical rodent models
• species variability
• xenogenicity

• Adipose tissue mesenchymal stem cells
• Conditioned medium
• Experimental autoimmune encephalomyelitis
• Immunomudulatory
• Regulatory T cells

• Adipose Tissue/cytology
• Animals
• Brain/immunology
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Culture Media, Conditioned/metabolism
• Cytokines/metabolism
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental/immunology
• Humans
• Immunomodulation
• Lymphocyte Activation
• Mesenchymal Stem Cells/immunology
• Mice
• Mice, Inbred C57BL
• Multiple Sclerosis/immunology
• T-Lymphocytes, Regulatory/immunology

• Rheumatoid arthritis
• adipocytokines
• adipose tissue
• inflammation
• myeloid cells
• treatment response
• weight loss

• adipogenesis
• endocrine disruptors
• immunomodulation
• mesenchymal stem cells
• tissue engineering
• tissue scaffolds

• P51 OD011104 NIH HHS

• apoptosis
• autophagy
• breast cancer
• conditioned media
• mesenchymal stem cells

• Cancer
• Chemokine
• Colorectal cancer
• Hematopoiesis
• Hypoxia
• Integrin
• MMP
• Microenvironment
• Niche
• Plasmin
• TGF-b
• Tissue-type plasminogen activator
• Wound healing
• uPA
• uPAR

• Cell Adhesion
• Cell Survival
• Cellular Microenvironment
• Disease Progression
• Mesenchymal Stem Cells/physiology
• Models, Biological
• Neoplasms/metabolism
• Neoplasms/pathology
• Plasminogen Activator Inhibitor 1/physiology
• Receptors, Urokinase Plasminogen Activator/physiology
• Regeneration
• Tumor Microenvironment
• Wound Healing

• Japan Society for the Promotion of Science and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)
• Naito Grant
• Grant-in-Aid for Scientific Research on Priority Areas from the MEXT
• Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT
• Program for Improvement of the Research Environment for Young Researchers funded by the Special Coordination Funds for Promoting Science and Technology of the MEXT, Japan

Alternative splicing was found to be a common phenomenon after the advent of whole transcriptome analyses or next generation sequencing. Over 90% of human genes were demonstrated to undergo at least one alternative splicing event. Alternative splicing is an effective mechanism to spatiotemporally expand protein diversity, which influences the cell fate and tissue development. The first focus of this review is to highlight recent studies, which demonstrated effects of alternative splicing on the differentiation of adipocytes. Moreover, use of evolving high-throughput approaches, such as transcriptome analyses (RNA sequencing), to profile adipogenic transcriptomes, is also addressed.

• adipogenesis
• alternative splicing
• splicing factor
• transcriptome analysis

• Adipocytes/cytology
• Adipocytes/metabolism
• Adipogenesis
• Alternative Splicing
• Animals
• Humans
• Organ Specificity
• RNA-Binding Proteins/metabolism

Maintenance of haematopoietic stem cells and differentiation of committed progenitors occurs in highly specialized niches. The interactions of haematopoietic stem and progenitor cells (HSPCs) with cells, growth factors and extracellular matrix (ECM) components of the bone marrow (BM) microenvironment control homeostasis of HSPCs. We only start to understand the complexity of the haematopoietic niche(s) that comprises endosteal, arterial, sinusoidal, mesenchymal and neuronal components. These distinct niches produce a broad range of soluble factors and adhesion molecules that modulate HSPC fate during normal hematopoiesis and BM regeneration. Adhesive interactions between HSPCs and the microenvironment will influence their localization and differentiation potential. In this review we highlight the current understanding of the functional role of ECM- and adhesion (regulating) molecules in the haematopoietic niche during homeostatic and regenerative hematopoiesis. This knowledge may lead to the improvement of current cellular therapies and more efficient development of future cellular products.

• BIGH3
• adhesion molecules
• bone marrow niche
• bone marrow regeneration
• differentiation
• extracellular matrix
• haematopoietic stem cells
• integrins
• matrix proteins
• periostin

Genomics experiments are widely acknowledged to produce a huge amount of data to be analysed. The challenge is to extract meaningful biological context for proteins or genes which is currently difficult because of the lack of an integrative workflow that hinders the efficiency and the robustness of data mining performed by biologists working on ruminants. Thus, we designed ProteINSIDE, a free web service (www.proteinside.org) that (I) provides an overview of the biological information stored in public databases or provided by annotations according to the Gene Ontology, (II) predicts proteins that are secreted to search for proteins that mediate signalisation between cells or tissues, and (III) analyses protein-protein interactions to identify proteins contributing to a process or to visualize functional pathways. Using lists of proteins or genes as a unique input, ProteINSIDE is an original all-in-one tool that merges data from these searches to present a fast overview and integrative analysis of genomic and proteomic data from Bovine, Ovine, Caprine, Human, Rat, and Murine species. ProteINSIDE was bench tested with 1000 proteins identifiers from each species by comparison with DAVID, BioMyn, AgBase, PrediSi, and Phobius. Compared to DAVID or BioMyn, identifications and annotations provided by ProteINSIDE were similar from monogastric proteins but more numerous and relevant for ruminants proteins. ProteINSIDE, thanks to SignalP, listed less proteins potentially secreted with a signal peptide than PrediSi and Phobius, in agreement with the low false positive rate of SignalP. In addition ProteINSIDE is the only resource that predicts proteins secreted by cellular processes that do not involve a signal peptide. Lastly, we reported the usefulness of ProteINSIDE to bring new biological hypotheses of research from proteomics data: the biological meaning of the uptake of adiponectin by the foetal muscle and a role for autophagy during ontogenesis of adipose and muscle tissues.

Obesity is a chronic disease that is associated with significantly increased levels of risk of a number of metabolic disorders. Despite these enhanced health risks, the worldwide prevalence of obesity has increased dramatically over the past few decades. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue, which is composed mostly of adipocytes. Thus, a deeper understanding of the regulation mechanism of adipose tissue and/or adipocytes can provide a clue for overcoming obesity-related metabolic diseases. In this review, we describe recent advances in the study of adipose tissue and/or adipocytes, focusing on proteomic approaches. In addition, we suggest future research directions for proteomic studies which may lead to novel treatments of obesity and obesity-related diseases.

• Adipocytes/metabolism
• Adipose Tissue/metabolism
• Animals
• Humans
• Lipid Metabolism
• Obesity/metabolism
• Protein Isoforms/metabolism
• Proteome/metabolism
• Proteomics/methods