Generation of oligodendroglial cells by direct lineage conversion

Nat Biotechnol. 2013 May;31(5):434-9. doi: 10.1038/nbt.2564. Epub 2013 Apr 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Fibroblasts / cytology*
  • Fibroblasts / physiology
  • Genetic Enhancement / methods
  • Mice
  • Myelin Sheath / metabolism*
  • Oligodendroglia / cytology*
  • Oligodendroglia / physiology*
  • Stem Cell Transplantation / methods
  • Stem Cells / cytology*
  • Stem Cells / physiology*
  • Transcription Factors / genetics*

Substances

  • Transcription Factors

Associated data

  • GEO/GSE40421