Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex.

The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX)(+) neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX(+) cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.
AuthorsChristophe Heinrich, Matteo Bergami, Sergio Gascón, Alexandra Lepier, Francesca Viganò, Leda Dimou, Bernd Sutor, Benedikt Berninger, Magdalena Götz
JournalStem cell reports (Stem Cell Reports) Vol. 3 Issue 6 Pg. 1000-14 (Dec 9 2014) ISSN: 2213-6711 [Electronic] United States
PMID25458895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • SOXB1 Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
  • Cell Proliferation
  • Cell Transdifferentiation (genetics)
  • Cellular Reprogramming (genetics)
  • Cerebral Cortex (cytology, injuries, metabolism)
  • Gene Expression
  • Mice
  • Neuroglia (cytology, metabolism)
  • Neurons (cytology, metabolism)
  • SOXB1 Transcription Factors (genetics, metabolism)
  • Synaptic Potentials (genetics)

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