New York Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Cell Stem Cell. 2010 Aug 6;7(2):163-73. doi: 10.1016/j.stem.2010.05.019.
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.
成体侧脑室下区(SVZ)中的神经祖细胞(NPCs)与室管膜和脉管龛相关,这些龛调节干细胞自我更新和分化。激活的 B 型干细胞及其祖细胞,即表达 EGFR 的短暂扩增型 C 细胞,与血管细胞的关联度最高,这表明该龛支持谱系进展。在这里,我们表明,增殖的 SVZ 祖细胞以基质衍生因子 1(SDF1)和 CXC 趋化因子受体 4(CXCR4)依赖的方式归巢到内皮细胞。我们表明,SDF1 在激活的 B 型和 C 型细胞中强烈地上调 EGFR 和 alpha6 整合素,增强它们的激活状态及其在血管龛中结合层粘连蛋白的能力。SDF1 增加了从 SVZ 迁移到嗅球的 A 型神经母细胞的迁移能力。因此,对 SDF1 的不同反应可以调节祖细胞对成年 SVZ 血管龛的占据和退出。