Heterogeneous Expression of SDF1 Retains Actively Proliferating Neural Progenitors in the Capillary Compartment of the Niche.
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.
['Zhu|Chang|C|', 'Mahesula|Swetha|S|', 'Temple|Sally|S|', 'Kokovay|Erzsebet|E|']
D000818:Animals D002196:Capillaries D049109:Cell Proliferation D054377:Chemokine CXCL12 D020547:Lateral Ventricles D051379:Mice D058953:Neural Stem Cells D055495:Neurogenesis D019718:Receptors, CXCR4 D015398:Signal Transduction D055153:Stem Cell Niche
SDF1 niche neural stem cells CXCR4 vasculature CXCL14 blood vessels