The Rb/E2F axis is a key regulator of the molecular signatures instructing the quiescent and activated adult neural stem cell state
Bensun C. Fong, Imane Chakroun, Mohamed Iqbal, Smitha Paul, Joseph Bastasic, Daniel O’Neil, Edward Yakubovich, Anthony T. Bejjani, Nastaran Ahmadi, Anthony Carter, Alysen Clark, Gustavo Leone, David S. Park, Noël Ghanem, Renaud Vandenbosch, Ruth S. Slack
Abstract
Long-term maintenance of the adult neurogenic niche depends on proper regulation of entry and exit from quiescence. Neural stem cell (NSC) transition from quiescence to activation is a complex process requiring precise cell-cycle control coordinated with transcriptional and morphological changes. How NSC fate transitions in coordination with the cell-cycle machinery remains poorly understood. Here we show that the Rb/E2F axis functions by linking the cell-cycle machinery to pivotal regulators of NSC fate. Deletion of Rb family proteins results in activation of NSCs, inducing a transcriptomic transition toward activation. Deletion of their target activator E2Fs1/3 results in intractable quiescence and cessation of neurogenesis. We show that the Rb/E2F axis mediates these fate transitions through regulation of factors essential for NSC function, including REST and ASCL1. Thus, the Rb/E2F axis is an important regulator of NSC fate, coordinating cell-cycle control with NSC activation and quiescence fate transitions.