人心肌再生能力非常弱，心肌受损后心脏无法自身修复。心肌细胞分裂增殖是心肌再生的关键，实验表明microRNA能够有效促进动物心肌细胞增殖，但哪些microRNA能够促进人源心肌细胞增殖还不清楚。人体多能干细胞在体外可以分化成心肌细胞，初始得到的心肌细胞增殖能力强，增殖能力随时间下降，这为我们提供了研究调控心肌细胞增殖的理想模型。我们通过系统分析人源心肌细胞microRNA动态表达谱，并结合实验筛选到了两个可以高效的促进心肌细胞增殖的microRNA。本项目拟在人源心肌细胞、斑马鱼和小鼠中过表达/敲低microRNA，进一步研究它们对心肌细胞增殖的促进作用以及对心肌细胞功能的影响，通过生物信息学和分子生物学手段鉴定它们的靶基因，并研究在心肌细胞中敲除靶基因是否也可以促进心肌细胞增殖，最后通过小鼠心梗模型研究过表达microRNA对心脏的治疗效果。本项目将为心梗的治疗提供新的靶标分子。

Human heart muscles have poor regeneration potential, and heart cannot repair itself after myocardial damage. Cardiomyocyte proliferation plays an important role in cardiac regeneration. Data reveals that microRNAs efficiently promote animal cardiac regeneration, but which microRNAs enable to promote human cardiomyocyte proliferation remains unknown. Human pluripotent stem cells can be differentiated into cardiomyocytes in vitro. The initial differentiated cardiomyocytes proliferate efficiently, but the proliferative capacity decreases with time, which offers us an ideal model to study cardiomyocyte proliferation. We systematically analyzed dynamic microRNA expression profiles, followed by experiments, and identified two microRNAs that enable to promote cardiomyocyte proliferation. We will further study the effects of microRNA overexpression/inhibition on cardiomyocyte proliferation and other functions in human cardiomyocytes, zebrafish and mouse. We will identify their target genes by bioinformatics and molecular biology techniques. We will investigate if target gene knockout can promote cardiomyocyte proliferation. Finally, we will investigate the effect of microRNA treatment on myocardial infarction mice. This project will offer novel molecular targets for the myocardial infarction therapy.