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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)1046-1061
Number of pages16
JournalStem cell reports
Volume8
Issue number4
Publication statusPublished - 11 Apr 2017
Peer-reviewedYes

External IDs

PubMed 28330621
ORCID /0000-0002-5304-4061/work/142238818

Keywords

Keywords

  • adult neurogenesis, astrogliogenesis, DICER, fate choice, hippocampus, microRNAs, mouse, neural stem cells, synergy

Library keywords