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
Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany.
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2243-E2252. doi: 10.1073/pnas.1614412114. Epub 2017 Feb 28.
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 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.
目前缺乏从人诱导多能干细胞（iPSC）快速高效生成少突胶质细胞（OL）的方案，但这可能是理解髓鞘疾病生物学特性以及开发此类疾病治疗方法的关键技术。在此，我们证明在iPSC来源的神经祖细胞中诱导三种转录因子（SOX10、OLIG2、NKX6.2）足以在28天内快速生成O4少突胶质细胞，效率高达70%，且整体基因表达谱与原代人少突胶质细胞相当。我们进一步证明，iPSC来源的少突胶质细胞在发育过程中和脱髓鞘后会分散并使小鼠中枢神经系统髓鞘化，适用于体外髓鞘化分析、疾病建模以及筛选可能促进少突胶质细胞分化的药理化合物。因此，本文提出的从iPSC生成少突胶质细胞的策略可能有助于研究人类髓鞘疾病以及开发用于药物发现的高通量筛选平台。
