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/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.
journal_name
Proc Natl Acad Sci U S Aauthors
Ehrlich M,Mozafari S,Glatza M,Starost L,Velychko S,Hallmann AL,Cui QL,Schambach A,Kim KP,Bachelin C,Marteyn A,Hargus G,Johnson RM,Antel J,Sterneckert J,Zaehres H,Schöler HR,Baron-Van Evercooren A,Kuhlmann Tdoi
10.1073/pnas.1614412114subject
Has Abstractpub_date
2017-03-14 00:00:00pages
E2243-E2252issue
11eissn
0027-8424issn
1091-6490pii
1614412114journal_volume
114pub_type
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