心脏冠状血管担负着重要的生理功能，先天性冠状血管畸形会导致恶性临床症状而冠状血管病变会导致冠心病等心脏疾病并最终发展为心力衰竭，因此关于冠状血管生长调控的知识具有重要的科学和医学意义。心外膜是包裹于心脏外表面的一层间皮结构，对冠状血管的发育负有重要的协助功能。转录组学数据显示心外膜细胞是一个异质性的群体，而现阶段研究者对于不同心外膜细胞亚群在冠状血管生长中的功能和工作机制仍然所知甚少。我们在前期工作中发现了一个新的由hapln4表达标记的心脏外膜细胞亚群，初步的研究发现在发育和再生过程中心脏冠状血管的生长可能接受hapln4+细胞的引导，而消除hapln4+细胞会影响冠状血管生长。这些结果提示冠状血管在发育和再生中的生长可能依赖于这个细胞亚群。在本申请中,我们计划探究hapln4+细胞的特性、引导冠状血管生长的功能以及与血管内皮细胞相互作用的分子机制。

The high mortality associated with congenital coronary artery anomalies and coronary artery disease makes the development of medical interventions that repair and replace diseased arteries a high priority for the cardiovascular research community. The epicardium is a mesothelial layer that envelopes outer surface of the heart. Recent studies in zebrafish and mice have highlighted the significant contributions of epicardial cells to heart repair. Extensive heterogeneity in epicardium has been revealed by transcriptome studies, while how different epicardial cell subpopulations benefitting cardiovascular repair is still poorly understood due to the lack of tools to mark and manipulate specific subpopulation. In preliminary studies, we identified a novel subpopulation of epicardial cell marked by the expression of hapln4. We found hapln4+ cells pioneer extending coronary vessels during development and rapidly accumulate on the wounded region prior to coronary revascularization. Our results also showed depleting hapln4+ cells block coronary vessel growth. The goal of this proposal is to address central questions about the function of this novel subpopulation of epicardial cell on coronary vessel growth and the molecular nature underlying the interaction between hapln4+ cell and coronary vessel endothelium cell. We believe the study proposed in this application will provide new knowledge about congenital heart diseases and new guidance and basis for the development of new strategies for cardiovascular regeneration.