Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
Open accessAbstract
Significance Understanding of myelin diseases and development of new treatment options are at least partly hampered by the limited availability of human oligodendrocytes. Induced pluripotent stem cells (iPSC) may be an ideal tool to circumvent this problem; however, rapid and efficient protocols to generate oligodendrocytes from human iPSC are currently lacking. The induction of the transcription factors SOX10, OLIG2, and NKX6.2 in iPSC-derived neural progenitors accelerates oligodendroglial differentiation significantly resulting in up to 70% of O4 + oligodendrocytes within 28 d. These oligodendrocytes myelinate the CNS during development and after demyelination, and are suitable for pharmacological screens and disease modeling. The strategy presented herein will markedly facilitate the studying of human myelin diseases and the development of screening platforms for drug discovery.
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Somatic cells such as fibroblasts or peripheral blood cells can be reprogrammed into iPS cells or directly converted into neural lineages, offering versatile platforms to model MS, PMD and other neuroinflammatory or demyelinating disorders.
“Somatic sources, such as fibroblasts or peripheral blood cells, can be reprogrammed into iPS cells or directly converted into neural lineages, offering versatile platforms to model MS, PMD and other neuroinflammatory or demyelinating disorders48–55.”
From From insights to innovations: evaluating preclinical paradigms in demyelinating disease therapeutics (2026) · cites this paper as [50]
The Abstract and Significance state that human iPSC-derived oligodendrocytes are suitable for modeling myelin diseases, and the Discussion reports direct conversion of mouse fibroblasts into oligodendrocyte progenitors. The paper does not establish peripheral blood cells as a source or describe direct conversion of human somatic cells; it also does not specifically demonstrate models of MS or PMD. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOligodendrocytes were derived from iPSCs as previously described.
“Oligodendrocytes were derived from iPSCs as previously described [17].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [17]
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- Authors
- Ehrlich, M., Mozafari, S., Glatza, M., Starost, L., Velychko, S., Hallmann, A.-L., Cui, Q.-L., Schambach, A., Kim, K.-P., Bachelin, C., Marteyn, A., Hargus, G., Johnson, R. M., Antel, J., Sterneckert, J., Zaehres, H., Schöler, H. R., Baron-Van Evercooren, A., & Kuhlmann, T.
- Affiliations
- University Hospital Münster (DE)
- Centre National de la Recherche Scientifique (FR)
- Max Planck Institute for Molecular Biomedicine (DE)
- Montreal Neurological Institute and Hospital (CA)
- Medizinische Hochschule Hannover (DE)
- McGill University (CA)
- Center for Regenerative Therapies Dresden (DE)
- University of Münster (DE)
- INSERM, U1127, F-75013 Paris, France;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-02-28
- Volume
- 114
- Issue
- 11
- Pages
- E2243-E2252
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5358375
- OpenAlex
- W2592644893
- Cited by
- 257
- References
- 51
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 26 · 2023: 25 · 2022: 39 · 2021: 28 · 2020: 35 · 2019: 31 · 2018: 19 · 2017: 5
- FWCI
- 10.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-INBS-0011)
- National Institute of Neurological Disorders and Stroke (R25NS070697)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- oligodendrocyte differentiation, induced pluripotent stem cells, transcription factors, SOX10, Olig2, NKX6-2, myelination, myelin diseases, demyelination, neural progenitor cells, disease modeling, drug discovery screening
- MeSH terms
- Ectopic Gene Expression, Animals, Brain, Cell Differentiation, Cells, Cultured, Demyelinating Diseases, Disease Models, Animal, Myelin Basic Protein, Humans, Mutation, Myelin Sheath, Oligodendroglia, Spinal Cord, Transcription Factors, Biomarkers, Cluster Analysis, tau Proteins, Cell Death, Oxidative Stress, Cell Lineage, Gene Expression Profiling, Mice, Induced Pluripotent Stem Cells, Neural Stem Cells, Transcriptome
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