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.
One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2 / K. Chanoumidou, B. Hernández-Rodríguez, F. Windener, C. Thomas, M. Stehling, S. Mozafari, S. Albrecht, L. Ottoboni, J. Antel, K. Kim, S. Velychko, Q.L. Cui, Y.K.T. Xu, G. Martino, J. Winkler, H.R. Schöler, A. Baron-Van Evercooren, O. Boespflug-Tanguy, J.M. Vaquerizas, M. Ehrlich, T. Kuhlmann. - In: STEM CELL REPORTS. - ISSN 2213-6711. - 16:4(2021 Apr 13), pp. 771-783. [10.1016/j.stemcr.2021.03.001]
One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2
L. Ottoboni;
2021
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.File | Dimensione | Formato | |
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