Lineage hierarchies and stochasticity ensure the long-term maintenance of adult neural stem cells

The cellular basis and extent of neural stem cell (NSC) self-renewal in adult vertebrates, and their heterogeneity, remain controversial. To explore the functional behavior and dynamics of individual NSCs within brain germinal pools, we combined genetic lineage tracing, quantitative clonal analysis, intravital imaging and global population assessments in the adult zebrafish telencephalon. We show that adult neurogenesis is organized in a hierarchy where a subpopulation of reservoir NSCs with longterm self-renewal potential generate a pool of operational NSCs taking stochastic fates biased towards neuronal differentiation. To fuel the long-term growth of the adult germinal niche, we provide evidence for the existence of an additional, upstream, progenitor population that supports the continuous generation of new reservoir NSCs, contributing to their overall expansion. Hence, the dynamics of vertebrate neurogenesis relies on a hierarchical organization where growth, self-renewal and neurogenic functions are segregated between different NSC types.