Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain

EMBO J. 2019 Sep 2;38(17):e100481. doi: 10.15252/embj.2018100481. Epub 2019 Jul 15.

Abstract

Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells.

Keywords: adult neurogenesis; miR-204; neural stem cells; neurogenesis; neurogenic priming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Cell Movement
  • Choroid Plexus / chemistry*
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Mice
  • MicroRNAs / cerebrospinal fluid
  • MicroRNAs / genetics*
  • Middle Aged
  • Neural Stem Cells / chemistry
  • Neural Stem Cells / cytology*
  • Stem Cell Niche

Substances

  • MIRN204 microRNA, human
  • MIRN204 microRNA, mouse
  • MicroRNAs

Associated data

  • GEO/GSE132217