In vivo reprogramming of astrocytes to neuroblasts in the adult brain

Nat Cell Biol. 2013 Oct;15(10):1164-75. doi: 10.1038/ncb2843. Epub 2013 Sep 22.

Abstract

Adult differentiated cells can be reprogrammed into pluripotent stem cells or lineage-restricted proliferating precursors in culture; however, this has not been demonstrated in vivo. Here, we show that the single transcription factor SOX2 is sufficient to reprogram resident astrocytes into proliferative neuroblasts in the adult mouse brain. These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged brains. When supplied with BDNF and noggin or when the mice are treated with a histone deacetylase inhibitor, iANBs develop into electrophysiologically mature neurons, which functionally integrate into the local neural network. Our results demonstrate that adult astrocytes exhibit remarkable plasticity in vivo, a feature that might have important implications in regeneration of the central nervous system using endogenous patient-specific glial cells.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Cell Proliferation
  • Cellular Reprogramming / genetics*
  • Glial Fibrillary Acidic Protein / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neural Stem Cells / cytology*
  • Neurons / cytology
  • Promoter Regions, Genetic / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Transcription Factors / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors