Flanagan Lisa A, Rebaza Liza M, Derzic Stanislava, Schwartz Philip H, Monuki Edwin S
Pathology Department, School of Medicine, University of California Irvine, California 92697-4800, USA.
J Neurosci Res. 2006 Apr;83(5):845-56. doi: 10.1002/jnr.20778.
Deciphering the factors that regulate human neural stem cells will greatly aid in their use as models of development and as therapeutic agents. The extracellular matrix (ECM) is a component of stem cell niches in vivo and regulates multiple functions in diverse cell types, yet little is known about its effects on human neural stem/precursor cells (NSPCs). We therefore plated human NSPCs on four different substrates (poly-L-ornithine, fibronectin, laminin, and matrigel) and compared their responses with those of mouse NSPCs. Compared with the other substrates, laminin matrices enhanced NSPC migration, expansion, differentiation into neurons and astrocytes, and elongation of neurites from NSPC-derived neurons. Laminin had a similar spectrum of effects on both human and mouse cells, highlighting the evolutionary conservation of NSPC regulation by this component of the ECM. Flow cytometry revealed that human NSPCs express on their cell surfaces the laminin-binding integrins alpha3, alpha6, alpha7, beta1, and beta4, and function-blocking antibodies to the alpha6 subunit confirmed a role for integrins in laminin-dependent migration of human NSPCs. These results define laminin and its integrin receptors as key regulators of human NSPCs.
解析调控人类神经干细胞的因素将极大地有助于其作为发育模型和治疗药物的应用。细胞外基质（ECM）是体内干细胞微环境的一个组成部分，可调节多种细胞类型的多种功能，但对其对人类神经干细胞/前体细胞（NSPCs）的影响却知之甚少。因此，我们将人类NSPCs接种在四种不同的基质（聚-L-鸟氨酸、纤连蛋白、层粘连蛋白和基质胶）上，并将它们的反应与小鼠NSPCs的反应进行比较。与其他基质相比，层粘连蛋白基质增强了NSPCs的迁移、扩增、向神经元和星形胶质细胞的分化以及NSPCs衍生神经元的神经突伸长。层粘连蛋白对人类和小鼠细胞具有相似的作用谱，突出了ECM的这一成分对NSPCs调控的进化保守性。流式细胞术显示，人类NSPCs在其细胞表面表达层粘连蛋白结合整合素α3、α6、α7、β1和β4，针对α6亚基的功能阻断抗体证实了整合素在人类NSPCs层粘连蛋白依赖性迁移中的作用。这些结果将层粘连蛋白及其整合素受体定义为人类NSPCs的关键调节因子。
