Quiescent neural stem cells transiently become neuron-like to coordinate long-range reactivation

Abstract Reactivation of quiescent neural stem cells (NSCs) in the central nervous system (CNS) is a tightly controlled process that generates new neurons and glia to maintain homeostasis or enable repair post-injury, but it remains unclear if reactivation of distinct NSC populations is coupled. Here, we discovered that NSC quiescence exit in Drosophila follows a hierarchical sequence, whereby activation of anterior stem cells in the brain lobes precedes and is required for the timely state-transition of more posterior NSCs in the ventral nerve cord. To achieve this, quiescent NSCs transiently activate neuronal genes. This transient neuronal state is temporary and specific to NSC dormancy, as neuronal genes are switched off after stem cells resume proliferation. Blocking neuronal firing in brain lobe neurons delays the onset of posterior NSC reactivation. Our results reveal long-range communication between quiescent NSCs to coordinate reactivation across the CNS, enabled by a transient, plastic neuron-like state that allows direct interaction with neuronal axons.