miR-17 similar to 92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

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 similar to 92 highly upregulated in activated NSCs and transit amplifying cells ( TACs) versus quiescent NSCs. Conditional miR-17 similar to 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 OLIG(2-) DLX2+ toward oligodendrogenic OLIG(2+) 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 similar to 92 deletion decreases proliferation and maturation. Together, these findings reveal multiple stage-specific functions of the miR-17 similar to 92 cluster within different adult V-SVZ lineages.