Kim Hyun Jung, Lee Eunsoo, Nam Myungwoo, Chung Jae Kwon, Joo Sunghoon, Nam Yoonkey, Sun Woong
Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejon 34141, Korea.
Exp Neurobiol. 2021 Aug 31;30(4):275-284. doi: 10.5607/en21012.
Neurogenesis persists in restricted regions of the adult brain, including the subventricular zone (SVZ). Adult neural stem cells (NSCs) in the SVZ proliferate and give rise to new neurons and glial cells depending on intrinsic and environmental cues. Among the multiple factors that contribute to the chemical, physical, and mechanical components of the neurogenic niche, we focused on the composition of the extracellular matrix (ECM) of vasculature and fractones in the SVZ. The SVZ consists of ECM-rich blood vessels and fractones during development and adulthood, and adult neural stem/progenitor cells (NS/PCs) preferentially attach to the laminin-rich basal lamina. To examine the ECM preference of adult NS/PCs, we designed a competition assay using cell micropatterning. Although both laminin and collagen type IV, which are the main components of basal lamina, act as physical scaffolds, adult NS/PCs preferred to adhere to laminin over collagen type IV. Interestingly, the ECM preference of adult NS/PCs could be manipulated by chemokines such as stromal-derived factor 1 (SDF1) and α6 integrin. As SDF1 re-routes NSCs and their progenitors toward the injury site after brain damage, these results suggest that the alteration in ECM preferences may provide a molecular basis for contextdependent NS/PC positioning.
神经发生在成人大脑的特定区域持续存在,包括脑室下区(SVZ)。SVZ中的成体神经干细胞(NSCs)会增殖,并根据内在和环境线索产生新的神经元和胶质细胞。在构成神经发生微环境的化学、物理和机械成分的多种因素中,我们重点关注了SVZ中脉管系统的细胞外基质(ECM)和分形子的组成。在发育和成年期,SVZ由富含ECM的血管和分形子组成,而成体神经干/祖细胞(NS/PCs)优先附着于富含层粘连蛋白的基膜。为了检测成体NS/PCs对ECM的偏好,我们设计了一种使用细胞微图案化的竞争试验。尽管作为基膜主要成分的层粘连蛋白和IV型胶原蛋白都起到物理支架的作用,但成体NS/PCs相对于IV型胶原蛋白更倾向于附着在层粘连蛋白上。有趣的是,成体NS/PCs对ECM的偏好可以被趋化因子如基质衍生因子1(SDF1)和α6整合素所调控。由于SDF1在脑损伤后会将NSCs及其祖细胞重新引导至损伤部位,这些结果表明ECM偏好的改变可能为依赖于上下文的NS/PC定位提供分子基础。