Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells
Research output: Contribution to journal › Research article › Contributed › peer-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 language | English |
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Pages (from-to) | 1046-1061 |
Number of pages | 16 |
Journal | Stem cell reports |
Volume | 8 |
Issue number | 4 |
Publication status | Published - 11 Apr 2017 |
Peer-reviewed | Yes |
External IDs
PubMed | 28330621 |
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ORCID | /0000-0002-5304-4061/work/142238818 |
Keywords
ASJC Scopus subject areas
Keywords
- adult neurogenesis, astrogliogenesis, DICER, fate choice, hippocampus, microRNAs, mouse, neural stem cells, synergy