转录因子Mesp1是调控人类多能干细胞心血管定向分化与心脏发育的关键分子，位于调控心血管细胞命运决定的转录层级之最高层。但由于其在早期心脏发育与分化过程中非常短暂的表达特性，其调控心血管细胞分化的具体机制尚未明确，与其相互结合的蛋白也未见报道。我们近期通过酵母双杂交实验，首次发现在人类多能干细胞心血管定向分化过程中，Mesp1可以与RNA结合蛋白Quaking直接结合。本项研究中，我们将进一步明确Quaking在人类多能干细胞心血管定向分化中的作用，探索Mesp1如何通过Quaking调控心血管定向分化相关mRNA的表达，阐明Mesp1结合Quaking调控人类多能干细胞心血管定向分化的分子机制，为提高人类多能干细胞分化为心血管细胞的效率，以及先天性心脏病的早期诊断防治提供理论依据。

Mesp1 is a master regulator for cardiovascular differentiation of pluripotent stem cells and mammalian heart development. It is at the top of the hierarchy of the gene network responsible for cardiovascular cell-fate determination. Owing to its transient expression nature during cardiac development and differentiation, however, the detailed mechanisms of Mesp1 regulating cardiovascular differentiation as well as its interacting proteins are unclear. Recently, using Mesp1 as the bait in a yeast two hybrid study, we have found that the RNA-binding protein Quaking directly interacts with Mesp1. In this proposed study, we will further confirm the roles of Quaking in directed cardiovsacular differentiation of human pluripotent stem cells. We will also investigate how Mesp1 regulates expressions of mRNAs related to cardiovascular differentiation through interacting with Quaking and clarify the detailed mechanisms of Mesp1 and Quaking in regulating cardiovascular differentiation. This will provide important information for improving the efficiency of cardiovascular differentiation for pluripotent stem cells as well as for early diagnosis and prevention of human congenital heart diseases.