title: Generation of oligodendroglial cells by direct lineage conversion.
abstract: Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. More importantly, iOPCs gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed myelin after transplantation into shiverer mice. We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: J Bradley
authors.initials: JB
authors.lastname: Zuchero
authors.forename: Henrik
authors.initials: H
authors.lastname: Ahlenius
authors.forename: Samuele
authors.initials: S
authors.lastname: Marro
authors.forename: Yi Han
authors.initials: YH
authors.lastname: Ng
authors.forename: Thomas
authors.initials: T
authors.lastname: Vierbuchen
authors.forename: John S
authors.initials: JS
authors.lastname: Hawkins
authors.forename: Richard
authors.initials: R
authors.lastname: Geissler
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
authors.forename: Marius
authors.initials: M
authors.lastname: Wernig
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D024861:Genetic Enhancement / Q000379:methods; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors