Continuous live imaging of adult neural stem cell division and lineage progression in vitro

Development. 2011 Mar;138(6):1057-68. doi: 10.1242/dev.061663.

Abstract

Little is known about the intrinsic specification of adult neural stem cells (NSCs) and to what extent they depend on their local niche. To observe adult NSC division and lineage progression independent of their niche, we isolated cells from the adult mouse subependymal zone (SEZ) and cultured them at low density without growth factors. We demonstrate here that SEZ cells in this culture system are primarily neurogenic and that adult NSCs progress through stereotypic lineage trees consisting of asymmetric stem cell divisions, symmetric transit-amplifying divisions and final symmetric neurogenic divisions. Stem cells, identified by their astro/radial glial identity and their slow-dividing nature, were observed to generate asymmetrically and fast-dividing cells that maintained an astro/radial glia identity. These, in turn, gave rise to symmetrically and fast-dividing cells that lost glial hallmarks, but had not yet acquired neuronal features. The number of amplifying divisions was limited to a maximum of five in this system. Moreover, we found that cell growth correlated with the number of subsequent divisions of SEZ cells, with slow-dividing astro/radial glia exhibiting the most substantial growth prior to division. The fact that in the absence both of exogenously supplied growth factors and of signals provided by the local niche neurogenic lineage progression takes place in such stereotypic fashion, suggests that lineage progression is, to a significant degree, cell intrinsic or pre-programmed at the beginning of the lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / drug effects
  • Adult Stem Cells / physiology*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cell Lineage / drug effects
  • Cell Lineage / physiology*
  • Cell Proliferation / drug effects
  • Cell Size / drug effects
  • Cell Tracking / methods*
  • Cells, Cultured
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mice
  • Nervous System / cytology
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology*
  • Time Factors

Substances

  • Intercellular Signaling Peptides and Proteins