胚胎干细胞肝向分化的力学-生物学耦合规律及其分子机制研究

项目名称： 胚胎干细胞肝向分化的力学-生物学耦合规律及其分子机制研究

项目编号： No.31470907

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 吕东媛

作者单位： 中国科学院力学研究所

项目金额： 85万元

中文摘要： 生物化学和力学环境的协同作用是影响干细胞分化的关键因素，然而力学因素（尤其是基于肝血窦特殊力学微环境）调控胚胎干细胞的肝向分化知之甚少。本项目以力学微环境调控胚胎干细胞肝向分化为科学问题，以基底硬度和拓扑结构等力学因素影响胚胎干细胞分化的规律及动力学为有限目标，拟建立耦合基底硬度和拓扑结构效应的新方法及力学可控的胚胎干细胞培养和分化新体系，结合细胞黏附动力学、实时动态观测技术研究基底硬度和拓扑结构对胚胎干细胞分化的影响规律及其分子调控机制，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。

中文关键词： 胚胎干细胞分化；肝细胞；基底硬度和拓扑结构；力学-生物学耦合；分子机制

英文摘要： The coupling of biochemical and mechanical signals determine embryonic stem cells (ESCs) differentiation. It remains unknown, however, how the mechanical factors (especially the characterized mechanical microenvironment of hepatic sinusoids) regulate the directed differentiation of ESCs to hepatocytes. This project attempts to address the scientific issue how mechanical environment modulates the differentiation from ESCs to hepatocyte. The specific aim is to quantify the impact and rule of substrate stiffness and topology on ESCs differentiation. A novel approach that coordinates the stiffness-topology coupling assay, the mechanically-controllable ESCs culture and differentiation system, cell adhesion dynamics and real-time dynamic observation technology is developed. Dynamics and molecular mechanisms of how substrate stiffness and topology affect the ESCs differentiation are studied to further the understandings of mechano-biological coupling of ESCs differentiation. The results enlighten new idea and methods in clinical liver disease treatment.

英文关键词： embryonic stem cells differentiation;hepatocytes;substrate stiffness and topology;coupling of mechanics and biology;molecular mechanisms