The atypical CDK activator RingoA/Spy1 regulates exit from quiescence in neural stem cells

In the adult mammalian brain, most neural stem cells (NSCs) are held in a reversible state of quiescence, which is essential to avoid NSC exhaustion and determine the appropriate neurogenesis rate. NSCs of the mouse adult subependymal niche provide neurons for olfactory circuits and can be found at different depths of quiescence, but very little is known on how their quiescence-to-activation transition is controlled. Here, we identify the atypical cyclin-dependent kinase (CDK) activator RingoA as a regulator of this process. We show that the expression of RingoA increases the levels of CDK activity and facilitates cell cycle entry of a subset of NSCs that divide slowly. Accordingly, RingoA-deficient mice exhibit reduced olfactory neurogenesis with an accumulation of quiescent NSCs. Our results indicate that RingoA plays an important role in setting the threshold of CDK activity required for adult NSCs to exit quiescence and may represent a dormancy regulator in adult mammalian tissues.© 2023 The Author(s)

Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis

Neural stem cells (NSCs) in the adult murine subependymal zone balance their self-renewal capacity and glial identity with the potential to generate neurons during the lifetime. Adult NSCs exhibit lineage priming via pro-neurogenic fate determinants. However, the protein levels of the neural fate determinants are not sufficient to drive direct differentiation of adult NSCs, which raises the question of how cells along the neurogenic lineage avoid different conflicting fate choices, such as self-renewal and differentiation. Here, we identify RNA-binding protein MEX3A as a post-transcriptional regulator of a set of stemness associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A regulates a quiescence-related RNA signature in activated NSCs that is needed for their return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A is a pivotal regulator of adult murine neurogenesis acting as a translational remodeller.© 2023. The Author(s)