Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells

TLDR

Neural stem cells reside in a vascular niche, yet no direct evidence has linked them functionally to blood vessel components. Endothelial coculture activates Notch and Hes1 signaling through enhanced neuroepithelial contact, driving neural stem cell self‑renewal. Endothelial cells secrete soluble factors that stimulate neural stem cell self‑renewal, suppress differentiation, and promote the generation of both projection neurons and interneurons, establishing endothelial cells as a critical component of the neural stem cell niche.

Abstract

Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.