Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors

Author:

Ehrlich Marc,Mozafari Sabah,Glatza Michael,Starost Laura,Velychko Sergiy,Hallmann Anna-Lena,Cui Qiao-Ling,Schambach Axel,Kim Kee-Pyo,Bachelin Corinne,Marteyn Antoine,Hargus Gunnar,Johnson Radia Marie,Antel Jack,Sterneckert Jared,Zaehres Holm,Schöler Hans R.,Baron-Van Evercooren Anne,Kuhlmann Tanja

Abstract

Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor cells is sufficient to rapidly generate O4+ OL with an efficiency of up to 70% in 28 d and a global gene-expression profile comparable to primary human OL. We further demonstrate that iPSC-derived OL disperse and myelinate the CNS of Mbpshi/shiRag−/− mice during development and after demyelination, are suitable for in vitro myelination assays, disease modeling, and screening of pharmacological compounds potentially promoting oligodendroglial differentiation. Thus, the strategy presented here to generate OL from iPSC may facilitate the studying of human myelin diseases and the development of high-throughput screening platforms for drug discovery.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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