In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Capacities of Sox2+ Neural Stem Cells in the Adult Hippocampus

Cell Stem Cell. 2007 Nov;1(5):515-28. doi: 10.1016/j.stem.2007.09.002.

Abstract

To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate-tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as at a single-cell level. A subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis.

Publication types

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

MeSH terms

  • Adult Stem Cells / metabolism*
  • Animals
  • Astrocytes / metabolism*
  • Cell Differentiation
  • Cell Lineage*
  • Cell Proliferation*
  • Cell Shape
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Gene Transfer Techniques
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism*
  • Lentivirus / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Multipotent Stem Cells / metabolism*
  • Neurons / metabolism*
  • Physical Exertion
  • Promoter Regions, Genetic
  • Retroviridae / genetics
  • SOXB1 Transcription Factors
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • HMGB Proteins
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Transcription Factors
  • Green Fluorescent Proteins