Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells

Stem Cell Reports. 2017 Apr 11;8(4):1046-1061. doi: 10.1016/j.stemcr.2017.02.012. Epub 2017 Mar 16.


Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs) are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs) has been unclear. As entry point to address that question we chose DICER, an endoribonuclease essential for miRNA biogenesis and other RNAi-related processes. By specific ablation of Dicer in aNSCs in vivo and in vitro, we demonstrate that miRNAs are required for the generation of new neurons, but not astrocytes, in the adult murine hippocampus. Moreover, we identify 11 miRNAs, of which 9 have not been previously characterized in neurogenesis, that determine neurogenic lineage fate choice of aNSCs at the expense of astrogliogenesis. Finally, we propose that the 11 miRNAs sustain adult hippocampal neurogenesis through synergistic modulation of 26 putative targets from different pathways.

Keywords: DICER; adult neurogenesis; astrogliogenesis; fate choice; hippocampus; microRNAs; mouse; neural stem cells; synergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Cells, Cultured
  • DEAD-box RNA Helicases / genetics
  • Gene Deletion
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurogenesis*
  • Neurons / cytology*
  • Neurons / metabolism
  • Ribonuclease III / genetics


  • MicroRNAs
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases