Directed differentiation of hippocampal stem/progenitor cells in the adult brain

Nat Neurosci. 2008 Aug;11(8):888-93. doi: 10.1038/nn.2148. Epub 2008 Jun 29.

Abstract

Adult neurogenesis is a lifelong feature of brain plasticity; however, the potency of adult neural stem/progenitor cells in vivo remains unclear. We found that retrovirus-mediated overexpression of a single gene, the bHLH transcription factor Ascl1, redirected the fate of the proliferating adult hippocampal stem/progenitor (AHP) progeny and lead to the exclusive generation of cells of the oligodendrocytic lineage at the expense of newborn neurons, demonstrating that AHPs in the adult mouse brain are not irrevocably specified in vivo. These data indicate that AHPs have substantial plasticity, which might have important implications for the potential use of endogenous AHPs in neurological disease.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Brain / cytology*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cell Lineage
  • Cell Survival / genetics
  • Cells, Cultured
  • Dentate Gyrus / cytology
  • Female
  • Gene Transfer Techniques
  • Genes, Reporter
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Hippocampus / cytology*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Lateral Ventricles / cytology
  • Mice
  • Mice, Inbred C57BL
  • Moloney murine leukemia virus / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / virology
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Oligodendroglia / virology
  • Rats
  • Species Specificity
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Stem Cells / virology
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • Antigens, Differentiation
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Transcription Factors
  • Green Fluorescent Proteins