Distinct Molecular Signatures of Quiescent and Activated Adult Neural Stem Cells Reveal Specific Interactions with Their Microenvironment

Stem Cell Reports. 2018 Aug 14;11(2):565-577. doi: 10.1016/j.stemcr.2018.06.005. Epub 2018 Jul 5.

Abstract

Deciphering the mechanisms that regulate the quiescence of adult neural stem cells (NSCs) is crucial for the development of therapeutic strategies based on the stimulation of their endogenous regenerative potential in the damaged brain. We show that LeXbright cells sorted from the adult mouse subventricular zone exhibit all the characteristic features of quiescent NSCs. Indeed, they constitute a subpopulation of slowly dividing cells that is able to enter the cell cycle to regenerate the irradiated niche. Comparative transcriptomic analyses showed that they express hallmarks of NSCs but display a distinct molecular signature from activated NSCs (LeX+EGFR+ cells). Particularly, numerous membrane receptors are expressed on quiescent NSCs. We further revealed a different expression pattern of Syndecan-1 between quiescent and activated NSCs and demonstrated its role in the proliferation of activated NSCs. Our data highlight the central role of the stem cell microenvironment in the regulation of quiescence in adult neurogenic niches.

Keywords: adult neurogenic niches; cell sorting; irradiation; microarray; neural stem cells; neurogenesis; quiescence; syndecan-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism*
  • Adult Stem Cells / radiation effects
  • Cell Cycle* / genetics
  • Cell Cycle* / radiation effects
  • Cell Differentiation* / genetics
  • Cell Differentiation* / radiation effects
  • Energy Metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / radiation effects
  • Neurogenesis
  • Oxidative Stress
  • Signal Transduction
  • Stem Cell Niche* / genetics
  • Stem Cell Niche* / radiation effects