Journal
STEM CELL REPORTS
Volume 12, Issue 1, Pages 6-13Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.11.022
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Funding
- NIH-NIA [R01 AG041861, P01AG19316]
- William and Ella Owens Research Foundation
- NIH-NCI [P30 CA54174, P30 CA054174-20]
- CTSA grant [UL1 TR001120]
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The vascular compartment of the adult brain ventricular-subventricular zone (V-SVZ) is a critical regulator of neural stem cell and progenitor function. Blood enters the V-SVZ via arteries and arterioles to capillaries that then connect with venules and veins to return blood to the heart. We found that stromal cell-derived factor 1 (SDF1) is expressed by a subpopulation of V-SVZ vessels, the capillaries, and that actively proliferating neural stem cells (NSCs) and progenitors are preferentially associated with these SDF1-positive vessels. In contrast, slowly dividing or quiescent NSCs are most prevalent near SDF1-negative vessels. By conditional knockout, we found that loss of SDF1 signaling in NSCs stimulates lineage progression and NSC displacement from the vessel niche. With aging, SDF1/CXCR4 signaling is dysregulated, coincident with reduced proliferation and increased displacement of dividing cells from the vasculature. Our findings demonstrate SDF1-based vascular heterogeneity in the niche and suggest that reduced SDF1 signaling contributes to age-related declines in adult neurogenesis.
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