Research in our lab focuses on the intrinsic and extrinsic regulation of stem cells in the adult mammalian brain. Using novel approaches to purify stem cells directly from their in vivo niche, we are defining the in vivo heterogeneity and potential of adult neural stem cells, and the gene regulatory networks underlying stem cell quiescence and activation. In addition, we are investigating how different compartments of the niche dynamically influence the behavior of adult neural stem cells and their progeny. These have revealed key roles of the physiological state, mediated by long-range diffusible signals and neural circuit innervation from distant brain regions, in the regulation of regionally distinct pools of stem cells. Thus, local and long-range global input act synergistically to regulate adult neural stem cells.