• adeno-associated virus
• cell reprogramming
• delivery systems
• lentivirus
• neurodegenerative diseases
• nonviral delivery

• NEUROD1
• T cell
• direct conversion
• scRNA-seq
• whole-genome bisulfite-seq

• Cellular Reprogramming
• Basic Helix-Loop-Helix Transcription Factors/metabolism
• Basic Helix-Loop-Helix Transcription Factors/genetics
• Kruppel-Like Factor 4
• Neurons/cytology
• Neurons/metabolism
• Animals
• Mice
• Induced Pluripotent Stem Cells/metabolism
• Induced Pluripotent Stem Cells/cytology
• Humans
• Blood Cells/cytology
• Blood Cells/metabolism
• Nerve Tissue Proteins/metabolism
• Nerve Tissue Proteins/genetics
• Cell Differentiation
• Fibroblasts/cytology

• 17bk0104016h0005 Japan Agency for Medical Research and Development (AMED)
• 17bm0609003h0006 Japan Agency for Medical Research and Development (AMED)
• 19bm0804003h0003 Japan Agency for Medical Research and Development (AMED)
• JP19bm0804014h0103 Japan Agency for Medical Research and Development (AMED)
• JP22bm0804023 Japan Agency for Medical Research and Development (AMED)
• JP17K10083 MEXT | Japan Society for the Promotion of Science (JSPS)
• JP20H03567 MEXT | Japan Society for the Promotion of Science (JSPS)
• JP22K18388 MEXT | Japan Society for the Promotion of Science (JSPS)
• JP23H02882 MEXT | Japan Society for the Promotion of Science (JSPS)
• JP26830018 MEXT | Japan Society for the Promotion of Science (JSPS)
• 24tm0524001h0002 Japan Agency for Medical Research and Development (AMED)

• aging
• cardiac muscles
• direct reprogramming
• partial reprogramming
• pioneer factors
• signaling
• skeletal muscle
• transdifferentiation

• P30 DK017047 NIDDK NIH HHS
• R01 DE033016 NIDCR NIH HHS

• direct reprogramming
• functional heterogeneity
• iNSC-derived neuron
• neural stem cells
• quality control
• single-cell RNA sequencing
• surrogate biomarker

• Humans
• Neurons
• Neural Stem Cells/metabolism
• Cell Differentiation/genetics
• Pluripotent Stem Cells
• Sequence Analysis, RNA

• 20171MFDS193, 22201MFDS122 Ministry of Food and Drug Safety

• FOXA2
• RA signaling
• SHH signaling
• human pluripotent stem cells
• serotonin neurons

• Humans
• Mice
• Animals
• Serotonin/metabolism
• Hedgehog Proteins/metabolism
• Neurons/metabolism
• Cell Differentiation/physiology
• Pluripotent Stem Cells/metabolism
• Hepatocyte Nuclear Factor 3-beta/genetics
• Hepatocyte Nuclear Factor 3-beta/metabolism

• 2021YFA1101300 National Key Research and Development Program of China
• 2017YFA0104100 National Key Research and Development Program of China
• 31771644 National Natural Science Foundation of China
• 81801331 National Natural Science Foundation of China
• 31930068 National Natural Science Foundation of China
• KYPT202204 Shanghai Yangzhi Rehabilitation Hospital talent introduction plan
• 22120230292 Fundamental Research Funds for the Central Universities
• National Key Research and Development Program of China
• National Natural Science Foundation of China
• Fundamental Research Funds for the Central Universities

• direct reprogramming
• nerve repair
• neurons
• spinal cord injury
• transdifferentiation

• Brain organoids
• Disease modeling
• Induced pluripotent stem cells (iPSCs)
• Neurons
• Transplantation therapy

• Humans
• Induced Pluripotent Stem Cells/physiology
• Brain
• Neurons
• Cell Differentiation
• Organoids/physiology

• ALS
• Alzheimer’s disease
• Huntington’s disease
• Parkinson’ disease
• cell reprogramming
• in vitro model

• Alzheimer's disease
• Brain disorders
• Brain region-specific transplantation
• Cognitive ability
• Neural subtype-specific transplantation
• Stem cell-based replacement therapy

• Ministry of Science and Technology of the People's Republic of China
• Chinese Academy of Sciences
• Xi’an Jiaotong-Liverpool University

In developed countries, the aging of the population and the associated increase in age-related diseases are causing major unresolved medical, social, and environmental matters. Therefore, research on aging has become one of the most important and urgent issues in life sciences. If the molecular mechanisms of the onset and progression of neurodegenerative diseases are elucidated, we can expect to develop disease-modifying methods to prevent neurodegeneration itself. Since the discovery of induced pluripotent stem cells (iPSCs), there has been an explosion of disease models using disease-specific iPSCs derived from patient-derived somatic cells. By inducing the differentiation of iPSCs into neurons, disease models that reflect the patient-derived pathology can be reproduced in culture dishes, and are playing an active role in elucidating new pathological mechanisms and as a platform for new drug discovery. At the same time, however, we are faced with a new problem: how to recapitulate aging in culture dishes. It has been pointed out that cells differentiated from pluripotent stem cells are juvenile, retain embryonic traits, and may not be fully mature. Therefore, attempts are being made to induce cell maturation, senescence, and stress signals through culture conditions. It has also been reported that direct conversion of fibroblasts into neurons can reproduce human neurons with an aged phenotype. Here, we outline some state-of-the-art insights into models of neuronal aging in vitro. New frontiers in which stem cells and methods for inducing differentiation of tissue regeneration can be applied to aging research are just now approaching, and we need to keep a close eye on them. These models are forefront and intended to advance our knowledge of the molecular mechanisms of aging and contribute to the development of novel therapies for human neurodegenerative diseases associated with aging.

• Japan Society for the Promotion of Science
• School of Medicine, Keio University

• GIVIMP
• ISO9001
• cell therapy
• genomic instability
• human pluripotent stem cells
• karyotype

• Cell Culture Techniques/methods
• Comparative Genomic Hybridization
• Genomic Instability
• Genomics
• Humans
• Pluripotent Stem Cells
• Reference Standards
• Reproducibility of Results
• Retrospective Studies

The reprogramming of cells into induced neural stem cells (iNSCs), which are faster and safer to generate than induced pluripotent stem cells, holds tremendous promise for fundamental and frontier research, as well as personalized cell-based therapies for neurological diseases. However, reprogramming cells with viral vectors increases the risk of tumor development due to vector and transgene integration in the host cell genome. To circumvent this issue, the Sendai virus (SeV) provides an alternative integration-free reprogramming method that removes the danger of genetic alterations and enhances the prospects of iNSCs from bench to bedside. Since pigs are among the most successful large animal models in biomedical research, porcine iNSCs (piNSCs) may serve as a disease model for both veterinary and human medicine. Here, we report the successful generation of piNSC lines from pig fibroblasts by employing the SeV. These piNSCs can be expanded for up to 40 passages in a monolayer culture and produce neurospheres in a suspension culture. These piNSCs express high levels of NSC markers (PAX6, SOX2, NESTIN, and VIMENTIN) and proliferation markers (KI67) using quantitative immunostaining and western blot analysis. Furthermore, piNSCs are multipotent, as they are capable of producing neurons and glia, as demonstrated by their expressions of TUJ1, MAP2, TH, MBP, and GFAP proteins. During the reprogramming of piNSCs with the SeV, no induced pluripotent stem cells developed, and the established piNSCs did not express OCT4, NANOG, and SSEA1. Hence, the use of the SeV can reprogram porcine somatic cells without first going through an intermediate pluripotent state. Our research produced piNSCs using SeV methods in novel, easily accessible large animal cell culture models for evaluating the efficacy of iNSC-based clinical translation in human medicine. Additionally, our piNSCs are potentially applicable in disease modeling in pigs and regenerative therapies in veterinary medicine.

Adult human multipotent neural cells (ahMNCs) are unique cells derived from adult human temporal lobes. They show multipotent differentiation potentials into neurons and astrocytes. In addition, they possess proangiogenic capacities. The objective of this study was to characterize ahMNCs in terms of expression of cell type-specific markers, in vitro differentiation potentials, and paracrine factors compared with several other cell types including fetal neural stem cells (fNSCs) to provide detailed molecular and functional features of ahMNCs. Interestingly, the expression of cell type-specific markers of ahMNCs could not be differentiated from those of pericytes, mesenchymal stem cells (MSCs), or fNSCs. In contrast, differentiation potentials of ahMNCs and fNSCs into neural cells were higher than those of other cell types. Compared with MSCs, ahMNCs showed lower differentiation capacities into osteogenic and adipogenic cells. Moreover, ahMNCs uniquely expressed higher levels of MCP-1 and GRO family paracrine factors than fNSCs and MSCs. These high levels of MCP-1 and GRO family mediated in vivo proangiogenic effects of ahMNCs. These results indicate that ahMNCs have their own distinct characteristics that could distinguish ahMNCs from other cell types. Characteristics of ahMNCs could be utilized further in the preclinical and clinical development of ahMNCs for regenerative medicine. They could also be used as experimental references for other cell types including fNSCs.

• astrocytes
• direct neuronal reprogramming
• epigenetics
• fibroblasts
• lineage conversion
• micro-RNA
• small molecules
• transcription factors

• dermal papilla cells
• dedifferentiation
• HaCaT cells
• small molecule inhibitors
• hair follicle regeneration
• three‑dimensional culture

Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of cell-based therapies; however, the safety and efficacy of potential iPSC-based treatments need to be verified in relevant animal disease models before their application in the clinic. Here, we report the derivation of iPSCs from common marmoset monkeys (Callithrix jacchus) using self-replicating mRNA vectors based on the Venezuelan equine encephalitis virus (VEE-mRNAs). By transfection of marmoset fibroblasts with VEE-mRNAs carrying the human OCT4, KLF4, SOX2, and c-MYC and culture in the presence of small molecule inhibitors CHIR99021 and SB431542, we first established intermediate primary colonies with neural progenitor-like properties. In the second reprogramming step, we converted these colonies into transgene-free pluripotent stem cells by further culturing them with customized marmoset iPSC medium in feeder-free conditions. Our experiments revealed a novel paradigm for flexible reprogramming of somatic cells, where primary colonies obtained by a single VEE-mRNA transfection can be directed either toward the neural lineage or further reprogrammed to pluripotency. These results (1) will further enhance the role of the common marmoset as animal disease model for preclinical testing of iPSC-based therapies and (2) establish an in vitro system to experimentally address developmental signal transduction pathways in primates.

• VEE-mRNA
• iPSCs
• marmoset
• nonhuman primate
• reprogramming

• Animals
• Biomarkers/metabolism
• Callithrix
• Cell Differentiation/drug effects
• Cell Differentiation/genetics
• Cell Lineage/genetics
• Cellular Reprogramming/drug effects
• Cellular Reprogramming/genetics
• Gene Expression Regulation/drug effects
• Induced Pluripotent Stem Cells/drug effects
• Induced Pluripotent Stem Cells/metabolism
• Karyotyping
• Kruppel-Like Factor 4
• Neurogenesis/drug effects
• Neurogenesis/genetics
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Small Molecule Libraries/pharmacology

Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical factors in the process of reprogramming human fibroblasts into neurons, such as safe and minimally invasive, it has a more promising application prospect. Therefore, this paper also summarizes some successful physical mechanisms of utilizing fibroblasts to acquire neurons, which will provide new ideas for somatic cell reprogramming.

• Human fibroblasts
• Neurons
• Physical factors
• Reprogramming
• Small molecules
• Transcriptional factors

Human keratinocytes and derived products are crucial for skin repair and regeneration. Despite substantial advances in engineered skin equivalents, their poor availability and immunorejection remain major challenges in skin grafting.

Induced keratinocyte-like cells (iKCs) were directly reprogrammed from human urine cells by retroviral transduction of two lineage-specific transcription factors BMI1 and △NP63α (BN). Expression of keratinocyte stem cell or their differentiation markers were assessed by PCR, immunofluorescence and RNA-Sequencing. Regeneration capacity of iKCs were assessed by reconstitution of a human skin equivalent under air-interface condition.

BN-driven iKCs were similar to primary keratinocytes (pKCs) in terms of their morphology, protein expression, differentiation potential, and global gene expression. Moreover, BN-iKCs self-assembled to form stratified skin equivalents in vitro.

This study demonstrated an approach to generate human iKCs that could be directly reprogrammed from human somatic cells and extensively expanded in serum- and feeder cell-free systems, which will facilitate their broad applicability in an efficient and patient-specific manner.

• Direct lineage reprogramming
• Induced keratinocyte-like cells
• Long-term expansion
• Skin reconstitution
• Urine cells

• Defined factors
• Direct conversion
• Human induced neural stem cells
• Robust and reproducible generation

Neural stem cells (NSCs) have garnered significant scientific and commercial interest in the last 15 years. Given their plasticity, defined as the ability to develop into different phenotypes inside and outside of the nervous system, with a capacity of almost unlimited self-renewal, of releasing trophic and immunomodulatory factors, and of exploiting temporal and spatial dynamics, NSCs have been proposed for (i) neurotoxicity testing; (ii) cellular therapies to treat CNS diseases; (iii) neural tissue engineering and repair; (iv) drug target validation and testing; (v) personalized medicine. Moreover, given the growing interest in developing cell-based therapies to target neurodegenerative diseases, recent progress in developing NSCs from human-induced pluripotent stem cells has produced an analog of endogenous NSCs. Herein, we will review the current understanding on emerging conceptual and technological topics in the neural stem cell field, such as deep characterization of the human compartment, single-cell spatial-temporal dynamics, reprogramming from somatic cells, and NSC manipulation and monitoring. Together, these aspects contribute to further disentangling NSC plasticity to better exploit the potential of those cells, which, in the future, might offer new strategies for brain therapies.

• cell engineering
• neural stem cell
• plasticity
• repair
• transplant

• Differentiation
• Hair follicle neural crest stem cells
• Motor neuron progenitor

• cell therapy
• cellular reprogramming
• direct conversion
• disease modeling
• induced neural stem cells
• induced pluripotent stem cells
• neuronal cells
• regionalization
• transdifferentiation
• transplantation

• Cell Differentiation/genetics
• Cellular Reprogramming/genetics
• Fibroblasts/metabolism
• Humans
• Induced Pluripotent Stem Cells/cytology
• Induced Pluripotent Stem Cells/metabolism
• Neural Stem Cells/cytology
• Neural Stem Cells/metabolism
• Neurons/cytology
• Neurons/metabolism

• I 3029 Austrian Science Fund FWF
• I 3029-B30 Austrian Science Fund
• EU through the ERA-NET E-RARE and JPND (MADGIC) research program
• Austrian Federal Ministry of Education, Science and Research (BMBWF)
• Austrian Science Fund

• Direct reprogramming
• Induced neuronal progenitor cells
• Parkinson's disease
• Pluripotency factors
• Reprogramming

• Alzheimer's disease
• cognitive improvement
• functional integration
• human induced neural progenitor cells
• synaptic networks

• Alzheimer Disease/etiology
• Alzheimer Disease/metabolism
• Alzheimer Disease/physiopathology
• Animals
• Biomarkers
• Cell Survival
• Cognitive Dysfunction
• Disease Models, Animal
• Fluorescent Antibody Technique
• Hippocampus/metabolism
• Hippocampus/physiopathology
• Humans
• Mice
• Mice, Transgenic
• Models, Biological
• Neural Stem Cells/metabolism
• Neuronal Plasticity
• Neurons/metabolism
• Synapses/metabolism

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

• direct conversion
• induced neural stem cells (iNSCs)
• neurological diseases
• reprogramming
• self-replicative mRNA
• small molecules

• Adult
• Animals
• Cells, Cultured
• Cellular Reprogramming
• Cellular Reprogramming Techniques/methods
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neural Stem Cells/cytology
• Neural Stem Cells/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Transgenes
• Urine/cytology

Scientific and technological advances of the past decade have shed light on the mechanisms underlying cell fate acquisition, including its transcriptional and epigenetic regulation during embryonic development. This knowledge has enabled us to purposefully engineer cell fates in vitro by manipulating expression levels of lineage-instructing transcription factors. Here, we review the state of the art in the cell programming field with a focus on the derivation of neural cells. We reflect on what we know about the mechanisms underlying fate changes in general and on the degree of epigenetic remodeling conveyed by the distinct reprogramming and direct conversion strategies available. Moreover, we discuss the implications of residual epigenetic memory for biomedical applications such as disease modeling and neuroregeneration. Finally, we cover recent developments approaching cell fate conversion in the living brain and define questions which need to be addressed before cell programming can become an integral part of translational medicine.

• Cell programming
• Direct conversion
• Disease modelling
• Forward programming
• In vivo conversion
• Transdifferentiation
• Translation
• Transplantation

• reprogramming
• transdifferentiation

• astrocytes
• differentiation
• glial restricted progenitor cells
• hindbrain
• oligodendrocytes

Direct reprogramming offers a unique approach by which to generate neural lineages for the study and treatment of neurological disorders. Our objective is to develop a clinically viable reprogramming strategy to generate neural precursor cells for the treatment of neurological disorders through cell replacement therapy. We initially developed a method for directly generating neural precursor cells (iNPs) from adult human fibroblasts by transient expression of the neural transcription factors, SOX2 and PAX6 using plasmid DNA. This study advances these findings by examining the use of chemically modified mRNA (cmRNA) for direct-to-iNP reprogramming. Chemically modified mRNA has the benefit of being extremely stable and non-immunogenic, offering a clinically suitable gene delivery system. The use of SOX2 and PAX6 cmRNA resulted in high co-transfection efficiency and cell viability compared with plasmid transfection. Neural positioning and fate determinant genes were observed throughout reprogramming with ion channel and synaptic marker genes detected during differentiation. Differentiation of cmRNA-derived iNPs generated immature GABAergic or glutamatergic neuronal phenotypes in conjunction with astrocytes. This represents the first time a cmRNA approach has been used to directly reprogram adult human fibroblasts to iNPs, potentially providing an efficient system by which to generate human neurons for both research and clinical application.

• Biotechnology
• Neuroscience
• Stem cell research

Recent reports suggest that induced neurons (iNs), but not induced pluripotent stem cell (iPSC)-derived neurons, largely preserve age-associated traits. Here, we report on the extent of preserved epigenetic and transcriptional aging signatures in directly converted induced neural stem cells (iNSCs). Employing restricted and integration-free expression of SOX2 and c-MYC, we generated a fully functional, bona fide NSC population from adult blood cells that remains highly responsive to regional patterning cues. Upon conversion, low passage iNSCs display a profound loss of age-related DNA methylation signatures, which further erode across extended passaging, thereby approximating the DNA methylation age of isogenic iPSC-derived neural precursors. This epigenetic rejuvenation is accompanied by a lack of age-associated transcriptional signatures and absence of cellular aging hallmarks. We find iNSCs to be competent for modeling pathological protein aggregation and for neurotransplantation, depicting blood-to-NSC conversion as a rapid alternative route for both disease modeling and neuroregeneration.

Induced neurons, but not induced pluripotent stem cell (iPSC)-derived neurons, preserve age-related traits. Here, the authors demonstrate that blood-derived induced neural stem cells (iNSCs), despite lacking a pluripotency transit, lose age-related signatures.

Autologous neural stem cells (NSCs) may offer a promising source for deriving dopaminergic (DA) cells for treatment of Parkinson's disease (PD).

Methods: By using Sendai virus, human peripheral blood mononuclear cells (PBMNCs) were reprogrammed to induced NSCs (iNSCs), which were then differentiated to dopaminergic neurons in vitro. Whole-genome deep sequencing was performed to search for mutations that had accumulated during the reprogramming and expansion processes. To find the optimal differentiation stage of cells for transplantation, DA precursors obtained at various differentiation time points were tested by engraftment into brains of naïve immunodeficient mice. At last, the safety and efficacy of iNSC-derived DA precursors were tested by transplantation into the striatum of immunodeficient PD mouse models.

Results: PBMNC-derived iNSCs showed similar characteristics to fetal NSCs, and were able to specifically differentiate to DA neurons with high efficiency in vitro. The sequencing data proved that no harmful SNVs, Indels and CNVs were generated during the reprogramming and expansion processes. DA precursors obtained between differentiation day 10 to 13 in vitro were most suitable for transplantation when a balanced graft survival and maturation were taken into account. Two weeks after transplantation of DA precursors into mouse PD models, the motor functions of PD mice started to improve, and continued to improve until the end of the experiments. No graft overgrowth or tumor was observed, and a significant number of A9-specific midbrain DA neurons were surviving in the striatum.

Conclusion: This study confirmed the efficacy of iNSC-derived DA precursors in a mouse PD model, and emphasized the necessity of genomic sequencing and vigorous safety assessment before any clinical translation using iNSCs.

• Parkinson's disease
• cell therapy
• genomic sequencing
• induced neural stem cells
• reprogramming

Neurodegenerative diseases are characterized by a gradual loss of cognitive and physical functions. Medications for these disorders are limited and treat the symptoms only. There are no disease-modifying therapies available, which have been shown to slow or stop the continuing loss of neurons. Transdifferentiation, whereby somatic cells are reprogrammed into another lineage without going through an intermediate proliferative pluripotent stem cell stage, provides an alternative strategy for regenerative medicine and disease modeling. In particular, the transdifferentiation of somatic cells into specific subset of patient-specific neuronal cells offers alternative autologous cell therapeutic strategies for neurodegenerative disorders and presents a rich source of using diverse somatic cell types for relevant applications in translational, personalized medicine, as well as human mechanistic study, new drug-target identification, and novel drug screening systems. Here, we provide a comprehensive overview of the recent development of transdifferentiation research, with particular attention to chemical-induced transdifferentiation and perspectives for modeling and treatment of neurodegenerative diseases.

• Cell signaling
• Extracellular matrix
• MicroRNA
• NSC
• Neural differentiation
• Stem cells
• Stem cells in clinical applications
• Transcription factor
• Transdifferenciation

• CRISPR/Cas9
• Cell model
• Gene editing
• Huntington disease
• Medium spiny neuron
• Stem cells
• Striatum

• Alzheimer's disease
• cell therapy
• gene therapy
• induced neurogenesis
• neprilysin
• tau

• disease modeling
• neuron regeneration
• neuronal degenerative
• neuronal differentiation
• neuronal trans-differentiation

• Cell Differentiation
• Cells, Cultured
• Neural Stem Cells
• Neurons
• Pluripotent Stem Cells

• cellular reprogramming
• chromatin remodeling
• exosome
• fibroblast
• neural progenitor
• ultrasound

• Cell Culture Techniques/methods
• Cell Differentiation
• Cell Line
• Cellular Reprogramming
• Cellular Reprogramming Techniques/methods
• Chromatin Assembly and Disassembly
• Exosomes/metabolism
• Fibroblasts/cytology
• Fibroblasts/metabolism
• Humans
• Neural Stem Cells/cytology
• Neural Stem Cells/metabolism
• Sonication

• cell metabolism
• experimental autoimmune encephalomyelitis
• inflammation
• macrophages
• microglia
• multiple sclerosis
• neural stem cells
• regenerative medicine
• stem cells
• succinate

• Animals
• Cell Line
• Central Nervous System/pathology
• Chronic Disease
• Dinoprostone/metabolism
• Female
• Humans
• Inflammation/pathology
• Macrophages/metabolism
• Mice, Inbred C57BL
• Neural Stem Cells/cytology
• Neural Stem Cells/transplantation
• Oxidative Phosphorylation
• Receptors, G-Protein-Coupled/metabolism
• Succinic Acid/cerebrospinal fluid
• Succinic Acid/metabolism

• MC_UU_00015/3 Medical Research Council
• MC_UU_12022/6 Medical Research Council
• MC_U105663142 Medical Research Council
• RRZA/057 RG79423 Wellcome Trust
• MR/K026682/1 Biotechnology and Biological Sciences Research Council
• 110159/Z/15/Z Wellcome Trust
• MR/K026682/1 Medical Research Council
• I 3029 Austrian Science Fund FWF
• Wellcome Trust
• 110158/Z/15/Z Wellcome Trust

• Neural stem cells
• Reprogramming
• Somatic cells
• Transdifferentiation

• Animals
• Cell Differentiation/genetics
• Cell Transdifferentiation/genetics
• Cellular Reprogramming/genetics
• Fibroblasts/cytology
• Humans
• Induced Pluripotent Stem Cells/transplantation
• Mice
• Neural Stem Cells/transplantation
• Neurodegenerative Diseases/therapy