Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells

Nat Biotechnol. 2013 May;31(5):426-33. doi: 10.1038/nbt.2561. Epub 2013 Apr 14.

Abstract

Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.

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/GSE45440