Quiescent neural stem cells transiently become 'neurons' to coordinate reactivation

Abstract

Reactivation of quiescent neural stem cells (qNSCs) is a coordinated process that generates new neurons and glia. Here, we show that during development reactivation follows a hierarchical sequence, whereby anteriorly located qNSCs control the reactivation of more posterior qNSCs in the central nervous system (CNS). Electrical communication between qNSCs and neurons enables this precise spatial and temporal control of reactivation throughout the entire span of the CNS. Using single-cell RNA-seq we discovered that, remarkably, qNSCs switch on a host of neuronal genes while maintaining a stem cell identity. This transient mixed identity is specific to qNSCs, as neuronal genes are turned off after stem cells resume proliferation. Our results uncover long-range communication between qNSCs to coordinate reactivation, enabled by a transient stem cell-neuron fate.