Neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) generate neurons and glia throughout life. MicroRNAs are important post-transcriptional regulators frequently acting in a context-dependent manner. Here, microRNA profiling defines cohorts of miRNAs in quiescent and activated NSCs, with miR-17∼92 highly upregulated in activated NSCs and transit amplifying cells (TACs) versus quiescent NSCs. Conditional miR-17∼92 deletion in the adult V-SVZ results in stage-specific effects. In NSCs, it reduces proliferation in vitro and in vivo, whereas in TACs, it selectively shifts neurogenic OLIG2 DLX2 toward oligodendrogenic OLIG2 DLX2 TACs, due to de-repression of an oligodendrogenic program, leading to increased oligodendrogenesis in vivo. This differential regulation of TAC subpopulations highlights the importance of TAC heterogeneity. Finally, in the NSC lineage for intraventricular oligodendrocyte progenitors, miR-17∼92 deletion decreases proliferation and maturation. Together, these findings reveal multiple stage-specific functions of the miR-17∼92 cluster within different adult V-SVZ lineages.
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| http://dx.doi.org/10.1016/j.celrep.2022.111773 | DOI Listing |
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Article Synopsis
- * NSCs in the V-SVZ have different states (quiescent or actively proliferating) and unique identities based on their specific locations, which leads to the production of various neuron and glia types.
- * The study emphasizes the need to understand how the diversity among NSCs affects brain plasticity and how the body communicates with these stem cells to influence their activity under different conditions.
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