Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling.
Neural progenitor cells (NPCs) in the adult subventricular zone (SVZ) are associated with ependymal and vasculature niches, which regulate stem cell self-renewal and differentiation. Activated Type B stem cells and their progeny, the transit-amplifying type C cells, which express EGFR, are most highly associated with vascular cells, indicating that this niche supports lineage progression. Here, we show that proliferative SVZ progenitor cells home to endothelial cells in a stromal-derived factor 1 (SDF1)- and CXC chemokine receptor 4 (CXCR4)-dependent manner. We show that SDF1 strongly upregulates EGFR and alpha6 integrin in activated type B and type C cells, enhancing their activated state and their ability to bind laminin in the vascular niche. SDF1 increases the motility of type A neuroblasts, which migrate from the SVZ toward the olfactory bulb. Thus, differential responses to SDF1 can regulate progenitor cell occupancy of and exit from the adult SVZ vascular niche.
Kokovay
Erzsebet
E
New York Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Goderie
Susan
S
Wang
Yue
Y
Lotz
Steve
S
Lin
Gang
G
Sun
Yu
Y
Roysam
Badrinath
B
Shen
Qin
Q
Temple
Sally
S
D000375:Aging / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001808:Blood Vessels / Q000166:cytology; D019070:Cell Lineage; D002552:Cerebral Ventricles / Q000098:blood supply* / Q000166:cytology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D042783:Endothelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016023:Integrins; D019718:Receptors, CXCR4; D066246:ErbB Receptors