Primitive neural stem cells in the adult mammalian brain give rise to GFAP-expressing neural stem cells

Stem Cell Reports. 2014 May 22;2(6):810-24. doi: 10.1016/j.stemcr.2014.04.008. eCollection 2014 Jun 3.

Abstract

Adult forebrain definitive neural stem cells (NSCs) comprise a subpopulation of GFAP-expressing subependymal cells that arise from embryonic fibroblast growth factor (FGF)-dependent NSCs that are first isolated from the developing brain at E8.5. Embryonic FGF-dependent NSCs are derived from leukemia inhibitory factor (LIF)-responsive, Oct4-expressing primitive NSCs (pNSCs) that are first isolated at E5.5. We report the presence of a rare population of pNCSs in the periventricular region of the adult forebrain. Adult-derived pNSCs (AdpNSCs) are GFAP(-), LIF-responsive stem cells that display pNSC properties, including Oct4 expression and the ability to integrate into the inner cell mass of blastocysts. AdpNSCs generate self-renewing, multipotent colonies that give rise to definitive GFAP(+) NSCs in vitro and repopulate the subependyma after the ablation of GFAP(+) NSCs in vivo. These data support the hypothesis that a rare population of pNSCs is present in the adult brain and is upstream of the GFAP(+) NSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Brain / metabolism*
  • Glial Fibrillary Acidic Protein
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Octamer Transcription Factor-3 / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • glial fibrillary astrocytic protein, mouse