The goal of this project is to determine the molecular basis of how the neuro-vascular interactions lead to their functional interdependence in tissue homeostasis. Given the importance of the vascular niche, the in vivo regulatory microenvironment, to support a variety of stem cells, it is surprising that the functional requirement of the vascular niche and the mechanisms involved in controlling the number of adult stem cells remains largely unknown. Our genetic ablation of endothelial capillaries in the neurogenic subventricular zone (SVZ) of adult brain has revealed the importance of the vascular niche in NSC maintenance. We have further performed extensive gene expression profiling in the SVZ vasculature (Lee et al. PLoS One 2012). We currently focus our in-depth functional experiments on investigating the role of soluble amyloid beta precursor protein (APP) as a vascular niche signal to maintain quiescence of NSCs. Understanding the mechanisms by which vascular niche signals maintain NSCs through the characterization of endothelial APP should be an essential prerequisite for the manipulation of NSCs for transplantation therapy of neurological diseases.
