Our genetic ablation of endothelial capillaries in the neurogenic subventricular zone (SVZ) of adult brain demonstrated the importance of the vascular niche in NSC maintenance. We utilize a systematic multi-faceted approach to identify and validate the vascular niche signals involved in maintenance, self-renewal, proliferation and differentiation of neural stem cells (Lee et al. PLoS One, 2012). a series of SVZ NSC culture experiments fully support the in vivo observation such that soluble endothelial signals support NSC survival but suppress NSC self-renewing growth. Further extensive gene expression profiling in the SVZ vasculature and in-depth functional experiments have revealed that soluble amyloid beta precursor protein (APP) secreted from SVZ endothelial cells may function as a vascular niche signal to maintain quiescence of NSCs (Manuscript under Review). We have also pursued studies in the molecular and cellular mechanisms underlying blood vessel and lymphatic vessel development in the central nervous system (CNS). We are interested in what signals control the CNS-specific vascular architecture and immune privileged microenvironment.
