Small Molecules Enable Highly Efficient Neuronal Conversion of Human Fibroblasts

Nat Methods. 2012 Jun;9(6):575-8. doi: 10.1038/nmeth.1972. Epub 2012 Apr 8.

Abstract

Forced expression of proneural transcription factors has been shown to direct neuronal conversion of fibroblasts. Because neurons are postmitotic, conversion efficiencies are an important parameter for this process. We present a minimalist approach combining two-factor neuronal programming with small molecule-based inhibition of glycogen synthase kinase-3β and SMAD signaling, which converts postnatal human fibroblasts into functional neuron-like cells with yields up to >200% and neuronal purities up to >80%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transdifferentiation*
  • Child, Preschool
  • Fibroblasts / physiology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Infant
  • Infant, Newborn
  • Neurons / physiology*
  • Signal Transduction / drug effects
  • Smad Proteins / antagonists & inhibitors
  • Transcription Factors / pharmacology

Substances

  • Smad Proteins
  • Transcription Factors
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3

Associated data

  • GEO/GSE36246