不同硬度基底细胞间、细胞-基底间黏附力对胚胎干细胞肝向分化的协同调控

The mechanism of mechanical response during stem cell differentiation is the core of how stiffness regulate differentiation from embryonic stem cells to hepatocytes. Cell adhesion is particularly important to regulate stem cell feeling and signal transduction in differentiation, and it has a typical physiological significance in embryonic development and histogenesis. The scientific issue of this project is to quantify the impact of adhesive force between cell-cell and cell-substrate which cooperative regulate the differentiation of embryonic stem cells to hepatocytes on different stiffness substrate. A novel approach that coordinates the stiffness assay, the mechanically-controlled embryonic stem cells culture and differentiation system, cell adhesive force measurement is developed to obtained cooperative regulation rule of quantitative adhesive force between cell-cell and cell-substrate and mechanical-biological coupling mechanism, especially the important regulation pathway YAP/TAZ. Adhesive force cooperative regulation and molecular mechanisms of how substrate stiffness affect the embryonic stem cells differentiation are studied to further the understandings of mechano-biological coupling of embryonic stem cells differentiation. The results will provide new idea and methods in clinical liver disease treatment.

干细胞分化过程中的力学响应机制是了解基底硬度（尤其是基于肝血窦特殊力学微环境）调控胚胎干细胞肝向分化的关键因素，分化过程中细胞黏附力对干细胞感受及力信号传递的协同调控影响尤为重要，在胚胎发育、组织发生中具有典型的生理意义。本项目以不同硬度基底影响胚胎干细胞肝向分化不同阶段细胞-细胞间及细胞-基底间黏附力对分化能力的协同调控为科学问题，建立基于肝脏生理硬度的水凝胶基底制备的新方法及力学可控的胚胎干细胞培养和分化新体系，通过量化细胞-细胞间和细胞-基底间黏附力分析两者的协同调控机制，重点揭示其中重要的调控通路YAP/TAZ的信号途径和重要机制，深化对胚胎干细胞分化力学-生物学耦合规律认识的同时为临床肝病治疗提供新的思路和方法。

干细胞分化过程中的力学响应机制是了解基底硬度（尤其是基于肝血窦特殊力学微环境）调控胚胎干细胞肝向分化的关键因素，分化过程中细胞黏附力对干细胞感受及力信号传递的协同调控影响尤为重要，在胚胎发育、组织发生中具有典型的生理意义。本项目以不同硬度基底影响胚胎干细胞肝向分化不同阶段细胞-细胞间及细胞-基底间黏附力及黏附蛋白对分化能力的协同调控为科学问题，建立了基于肝脏生理硬度的水凝胶基底制备的新方法及力学可控的胚胎干细胞培养和分化新体系，通过量化细胞-细胞间和细胞-基底间黏附力及黏附蛋白表达分析两者的协同调控机制，重点研究了YAP的信号途径和重要机制，深化对胚胎干细胞分化力学-生物学耦合规律认识的同时为临床肝病治疗提供新的思路和方法。