Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells
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.
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We thank H. Singer for VSM cells, Y.-P. Hseuh for Tbr1 antibody, and C. Fasano, Y. Wang, C. Butler, and K. Kirchofer for help in manuscript preparation. Supported by the National Institute of Neurological Disorders and Stroke and the New York State spinal cord research program.
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Science
Volume 304 | Issue 5675
28 May 2004
28 May 2004
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American Association for the Advancement of Science.
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Received: 9 January 2004
Accepted: 19 March 2004
Published in print: 28 May 2004
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