| Literature DB >> 28246330 |
Marc Ehrlich1,2, Sabah Mozafari3,4,5,6, Michael Glatza2, Laura Starost1,2, Sergiy Velychko2, Anna-Lena Hallmann1,2, Qiao-Ling Cui7, Axel Schambach8, Kee-Pyo Kim2, Corinne Bachelin3,4,5,6, Antoine Marteyn3,4,5,6, Gunnar Hargus1,2, Radia Marie Johnson9, Jack Antel7, Jared Sterneckert10, Holm Zaehres2,11, Hans R Schöler2,12, Anne Baron-Van Evercooren3,4,5,6, Tanja Kuhlmann13.
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.Entities:
Keywords: disease modeling; forward patterning; human iPSC; myelination; oligodendrocytes
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Year: 2017 PMID： 28246330 PMCID： PMC5358375 DOI： 10.1073/pnas.1614412114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205