One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2
Chanoumidou K, Hernández-Rodríguez B, Windener F, Thomas C, Stehling M, Mozafari S, Albrecht S, Ottoboni L, Antel J, Kim KP, Velychko S, Cui QL, Xu YKT, Martino G, Winkler J, Schöler HR, Baron-Van Evercooren A, Boespflug-Tanguy O, Vaquerizas JM, Ehrlich M, Kuhlmann T (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 16
Pages Range: 771-783
Journal Issue: 4
DOI: 10.1016/j.stemcr.2021.03.001
Abstract
Limited access to human oligodendrocytes impairs better understanding of oligodendrocyte pathology in myelin diseases. Here, we describe a method to robustly convert human fibroblasts directly into oligodendrocyte-like cells (dc-hiOLs), which allows evaluation of remyelination-promoting compounds and disease modeling. Ectopic expression of SOX10, OLIG2, and NKX6.2 in human fibroblasts results in rapid generation of O4+ cells, which further differentiate into MBP+ mature oligodendrocyte-like cells within 16 days. dc-hiOLs undergo chromatin remodeling to express oligodendrocyte markers, ensheath axons, and nanofibers in vitro, respond to promyelination compound treatment, and recapitulate in vitro oligodendroglial pathologies associated with Pelizaeus-Merzbacher leukodystrophy related to PLP1 mutations. Furthermore, DNA methylome analysis provides evidence that the CpG methylation pattern significantly differs between dc-hiOLs derived from fibroblasts of young and old donors, indicating the maintenance of the source cells’ “age.” In summary, dc-hiOLs represent a reproducible technology that could contribute to personalized medicine in the field of myelin diseases.
Authors with CRIS profile
Involved external institutions
Max-Planck-Institut für molekulare Biomedizin / Max Planck Institute for Molecular Biomedicine
Germany (DE)
Universitätsklinikum Münster
Germany (DE)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
France (FR)
Hôpital Universitaire Robert-Debré
France (FR)
Montreal Neurological Institute and Hospital (MNI, The Neuro)
Canada (CA)
Università Vita-Salute San Raffaele (UniSR)
Italy (IT)
Johns Hopkins University (JHU)
United States (USA) (US)
Germany (DE)
Universitätsklinikum Münster
Germany (DE)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
France (FR)
Hôpital Universitaire Robert-Debré
France (FR)
Montreal Neurological Institute and Hospital (MNI, The Neuro)
Canada (CA)
Università Vita-Salute San Raffaele (UniSR)
Italy (IT)
Johns Hopkins University (JHU)
United States (USA) (US)
How to cite
APA:
Chanoumidou, K., Hernández-Rodríguez, B., Windener, F., Thomas, C., Stehling, M., Mozafari, S.,... Kuhlmann, T. (2021). One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2. Stem Cell Reports, 16(4), 771-783. https://dx.doi.org/10.1016/j.stemcr.2021.03.001
MLA:
Chanoumidou, Konstantina, et al. "One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2." Stem Cell Reports 16.4 (2021): 771-783.
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