Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
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DOI：
10.1073/pnas.1614412114
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发表时间：
2017-03-14
影响因子：
11.1
通讯作者：
Kuhlmann, Tanja
中科院分区：
文献类型：
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作者：
Ehrlich, Marc;Mozafari, Sabah;Kuhlmann, Tanja
目前缺乏从人诱导多能干细胞（iPSC）产生少突胶质细胞（OL）的快速有效的方案，但可能是了解髓鞘疾病生物学和开发此类疾病治疗方法的关键技术。在这里，我们证明了在iPSC衍生的神经祖细胞中诱导三种转录因子（SOX 10，OLIG 2，NKX6.2）足以快速产生O 4（+）OL，28 d内效率高达70%，并且与原代人类OL的整体基因表达谱相当。我们进一步证明了iPSC衍生的OL在发育期间和脱髓鞘后分散Mbp（shi/shi）Rag（-/-）小鼠的CNS并使其髓鞘化，适用于体外髓鞘形成测定、疾病建模和筛选可能促进少突胶质细胞分化的药理学化合物。因此，本文提出的从iPSC产生OL的策略可能有助于人类髓鞘疾病的研究和药物发现高通量筛选平台的开发。
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.