Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
Stem Cell Reports. 2019 Jan 8;12(1):6-13. doi: 10.1016/j.stemcr.2018.11.022. Epub 2018 Dec 27.
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.
成人脑室下区（V-SVZ）的血管区室是神经干细胞和祖细胞功能的关键调节者。血液通过动脉和小动脉进入 V-SVZ 的毛细血管，然后与小静脉和静脉连接，将血液回流到心脏。我们发现基质细胞衍生因子 1（SDF1）由 V-SVZ 血管的一部分表达，即毛细血管，并且活跃增殖的神经干细胞（NSC）和祖细胞优先与这些 SDF1 阳性血管相关。相比之下，缓慢分裂或静止的 NSCs 最常见于 SDF1 阴性血管附近。通过条件性基因敲除，我们发现 NSCs 中 SDF1 信号的缺失会刺激谱系进展和 NSC 从血管龛中移位。随着年龄的增长，SDF1/CXCR4 信号失调，与增殖减少和分裂细胞从血管中移位增加同时发生。我们的研究结果表明龛位中基于 SDF1 的血管异质性，并表明 SDF1 信号的减少导致与年龄相关的成年神经发生下降。
