Quiescence as an Active and Dynamic Regulator of Neural Stem Cells in Adult Olfactory Neurogenesis.

Adult olfactory neurogenesis depends largely on the persistence of resident quiescent neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) and their capacity to reversibly switch to an activated state to generate new neurons. These cells exhibit reduced cell-cycle and biosynthetic activity while maintaining key signaling and stress-response programs. Rather than representing a uniform condition, quiescence encompasses a continuum of substates, ranging from deep to shallow, each characterized by distinct activation thresholds. The dynamics and reversibility of state transitions are regulated by interactions between NSCs and neighboring cells, the extracellular matrix, and systemic factors, among others. With aging, NSCs progressively shift toward deeper quiescent states that are less permissive to activation, thereby reducing overall neurogenic output. Consequently, quiescence should no longer be regarded as a passive pause in stem cell activity, but an organizing principle that underlies the long-term maintenance and adaptability of adult NSCs. A deeper understanding of how quiescence is established, diversified, and dynamically regulated will be essential for elucidating the principles governing adult olfactory neurogenesis and for harnessing its regenerative potential in aging and disease.