https://ror.org/00rs6vg23 Department of Psychology, College of Arts and Sciences, The Ohio State University, Columbus, OH, USA.
https://ror.org/00rs6vg23 Neuroscience Graduate Program, The Ohio State University, Columbus, OH, USA.
Life Sci Alliance. 2024 Apr 17;7(7). doi: 10.26508/lsa.202402659. Print 2024 Jul.
The vasculature is a key component of adult brain neural stem cell (NSC) niches. In the adult mammalian hippocampus, NSCs reside in close contact with a dense capillary network. How this niche is maintained is unclear. We recently found that adult hippocampal NSCs express VEGF, a soluble factor with chemoattractive properties for vascular endothelia. Here, we show that global and NSC-specific VEGF loss led to dissociation of NSCs and their intermediate progenitor daughter cells from local vasculature. Surprisingly, though, we found no changes in local vascular density. Instead, we found that NSC-derived VEGF supports maintenance of gene expression programs in NSCs and their progeny related to cell migration and adhesion. In vitro assays revealed that blockade of VEGF receptor 2 impaired NSC motility and adhesion. Our findings suggest that NSCs maintain their own proximity to vasculature via self-stimulated VEGF signaling that supports their motility towards and/or adhesion to local blood vessels.
血管系统是成年大脑神经干细胞（NSC）龛的关键组成部分。在成年哺乳动物海马体中，NSC 与密集的毛细血管网络紧密接触。目前尚不清楚这种龛位是如何维持的。我们最近发现，成年海马体 NSC 表达 VEGF，这是一种具有趋化性的可溶性因子，可吸引血管内皮细胞。在这里，我们表明，全局和 NSC 特异性 VEGF 缺失导致 NSCs 及其中间祖细胞与局部血管分离。但令人惊讶的是，我们没有发现局部血管密度的变化。相反，我们发现 NSC 衍生的 VEGF 支持与细胞迁移和黏附相关的 NSCs 及其祖细胞的基因表达程序的维持。体外实验表明，VEGF 受体 2 的阻断会损害 NSC 的迁移和黏附能力。我们的研究结果表明，NSC 通过自我刺激的 VEGF 信号维持其与血管的接近度，从而支持其向局部血管迁移和/或黏附的能力。
