251. Adult SVZ Lineage Cells Home to and Leave the Vascular Niche via Differential Responses to SDF1/CXCR4 Signaling
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Erzsebet Kokovay, Yue Wang, Susan K. Goderie, Qin Shen, Sally Temple, Gang Lin, Steven Lotz, Badrinath Roysam, and Yu Sun
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Aging ,Integrins ,Receptors, CXCR4 ,Subventricular zone ,Biology ,Lymphocyte Activation ,Models, Biological ,CXCR4 ,Article ,Cerebral Ventricles ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Neuroblast ,medicine ,Genetics ,Animals ,Cell Lineage ,CXC chemokine receptors ,Progenitor cell ,030304 developmental biology ,Neurons ,B-Lymphocytes ,0303 health sciences ,Chemotaxis ,Stem Cells ,Endothelial Cells ,Cell Biology ,STEMCELL ,Chemokine CXCL12 ,Neural stem cell ,Olfactory bulb ,Cell biology ,ErbB Receptors ,medicine.anatomical_structure ,nervous system ,Blood Vessels ,Molecular Medicine ,Stem cell ,030217 neurology & neurosurgery ,Signal Transduction ,Stem Cell Transplantation - Abstract
SummaryNeural 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 α6 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.
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