One-step Reprogramming of Human Fibroblasts into Oligodendrocyte-like Cells by SOX10, OLIG2, and NKX6.2
Konstantina Chanoumidou, Benjamín Hernández-Rodríguez, Farina Windener, Christian Thomas, Martin Stehling, Sabah Mozafari, Stefanie Albrecht, Linda Ottoboni, Jack P. Antel, Kee-Pyo Kim, Sergiy Velychko, Qiao Ling Cui, Yu Kang T. Xu, Gianvito Martino, Jürgen Winkler, Hans R. Schöler, Anne Baron‐Van Evercooren, Odile Boespflug‐Tanguy, Juan M. Vaquerizas, Marc Ehrlich, Tanja Kuhlmann
Abstract
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.