Proc Natl Acad Sci U S A. 2017 Feb 28. pii: 201614412. doi: 10.1073/pnas.1614412114. [Epub ahead of print]

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

Ehrlich M^1,2, Mozafari S^3,4,5,6, Glatza M², Starost L^1,2, Velychko S², Hallmann AL^1,2, Cui QL⁷, Schambach A⁸, Kim KP², Bachelin C^3,4,5,6, Marteyn A^3,4,5,6, Hargus G^1,2, Johnson RM⁹, Antel J⁷, Sterneckert J¹⁰, Zaehres H^2,11, Schöler HR^2,12, Baron-Van Evercooren A^3,4,5,6, Kuhlmann T¹³.

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 Mbp^shi/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.