Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Cell Stem Cell. 2012 Aug 3;11(2):220-30. doi: 10.1016/j.stem.2012.06.016.
Neurons arise in the adult forebrain subventricular zone (SVZ) from Type B neural stem cells (NSCs), raising considerable interest in the molecules that maintain this life-long neurogenic niche. Type B cells are anchored by specialized apical endfeet in the center of a pinwheel of ependymal cells. Here we show that the apical endfeet express high levels of the adhesion and signaling molecule vascular cell adhesion molecule-1 (VCAM1). Disruption of VCAM1 in vivo causes loss of the pinwheels, disrupted SVZ cytoarchitecture, proliferation and depletion of the normally quiescent apical Type B cells, and increased neurogenesis in the olfactory bulb, demonstrating a key role in niche structure and function. We show that VCAM1 signals via NOX2 production of reactive oxygen species (ROS) to maintain NSCs. VCAM1 on Type B cells is increased by IL-1β, demonstrating that it can act as an environmental sensor, responding to chemokines involved in tissue repair.
成年大脑室下区 (SVZ) 的神经元由 B 型神经干细胞 (NSCs) 产生，这引起了人们对维持这种终身神经发生龛的分子的极大兴趣。B 型细胞通过其特化的顶端足锚定于室管膜细胞轮辐的中心。在这里，我们发现顶端足表达高水平的黏附和信号分子血管细胞黏附分子-1 (VCAM1)。体内破坏 VCAM1 会导致轮辐消失、SVZ 细胞结构紊乱、正常静止的顶端 B 型细胞增殖和耗竭，以及嗅球中的神经发生增加，这表明其在龛位结构和功能中发挥关键作用。我们发现 VCAM1 通过产生活性氧 (ROS) 的 NOX2 信号来维持 NSCs。B 型细胞上的 VCAM1 被白细胞介素-1β增加，表明它可以作为环境传感器，对参与组织修复的趋化因子做出反应。
