Direct reprogramming of fibroblasts into neural stem cells by defined factors

Cell Stem Cell. 2012 Apr 6;10(4):465-72. doi: 10.1016/j.stem.2012.02.021. Epub 2012 Mar 22.

Abstract

Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity-which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Cell Dedifferentiation*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation / genetics
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Antigens, Differentiation
  • Transcription Factors

Associated data

  • GEO/GSE30500