Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Sci Signal. 2012 Jun 5;5(227):ra41. doi: 10.1126/scisignal.2003002.
Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood. We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase-activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.
驻留干细胞和前体细胞的选择性增殖、分化为目标体细胞类型，以及空间形态组织。机械环境在协调这些过程中的作用还知之甚少。我们表明，来源于天然心脏组织的多能细胞持续监测细胞基底的刚性，并在细胞基底的刚性与心肌非常匹配时表现出增强的增殖、内皮分化和形态发生。这些不同过程的机械调节需要 p190RhoGAP，它是 RhoA 的鸟苷三磷酸酶激活蛋白，通过 RhoA 依赖和非依赖机制发挥作用。p190RhoGAP 的丰度自然或诱导性降低，通过将细胞-细胞和细胞-基底相互作用与控制分化的遗传电路相耦合，触发了一系列发育事件。
