文章基本信息

标题：Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
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作者：Marc Ehrlich ; Sabah Mozafari ; Michael Glatza 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：11
页码：E2243-E2252
DOI：10.1073/pnas.1614412114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 Mbp ^shi/shi Rag ^−/− 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.
关键词：human iPSC ; oligodendrocytes ; forward patterning ; myelination ; disease modeling