Adult neurogenic niches harbor quiescent neural stem cells; however, their invivo identity has been elusive. Here, we prospectively isolate GFAP+CD133+ (quiescent neural stem cells [qNSCs]) and GFAP+CD133+EGFR+ (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro. In contrast, qNSCs are largely dormant in vivo, generate olfactorybulb interneurons with slower kinetics, and only rarelyform colonies invitro. Moreover, qNSCs are Nestin negative, a marker widely used for neural stem cells.Upon activation, qNSCs upregulate Nestin and EGFR and become highly proliferative. Notably, qNSCs and aNSCs can interconvert invitro. Transcriptome analysis reveals that qNSCs share features with quiescent stem cells from other organs. Finally, small-molecule screening identified the GPCR ligands, S1P and PGD2, as factors that actively maintain the quiescent state of qNSCs.
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