Journal
STEM CELLS AND DEVELOPMENT
Volume 26, Issue 16, Pages 1199-1213Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2016.0350
Keywords
neural stem cells; vascular niche; shear stress; neurogenesis; oligodendrocytes
Funding
- New York State Department of Health NYSTEM [C026419- DMT]
- National Institutes of Health [RO1AG041861-ST]
- National Science Foundation [CBET-1350240- GD]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1737130] Funding Source: National Science Foundation
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The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.
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