非编码RNA在心肌细胞形成中的作用与调控机制

定向分化和转分化获得心肌细胞是治疗心脏疾病的前沿研究，但分化的低效和安全性仍受争议。非编码RNA（ncRNA）在细胞命运转变中具有重要作用，但心肌细胞形成中ncRNA的作用及其介导的调控网络尚不明确。我们将利用心肌细胞形成的体内外模型与ncRNA调控细胞命运研究方面的特长，结合生物信息分析系统筛查可能调控心肌细胞关键转录因子和信号通路的心肌特异性ncRNA，并进一步明确lncRNA-TPB等在心肌细胞形成中的功能，通过报告基因、RNA pull-down、RIP等实验阐明ncRNA在心肌细胞形成中的具体调控机制。在此基础上，将新发现的ncRNA介入到心肌细胞体内转分化模型中，分析关键ncRNA对体内心肌细胞转分化效率和心脏功能回复等方面的影响。本项目的完成，将更加丰富心肌细胞形成中ncRNA介导的表观遗传特异调控网络，为高效获得高质量心肌细胞及其早日安全用于疾病治疗提供重要依据和新靶点。

To obtain cardiomyocytes by direct differentiation and transdifferentiation is the most promising frontier for the treatment of heart diseases, but the low efficiency and safety of transdifferentiation are still controversial. Non-coding RNA plays critical function in cell fate transition, but it is not clear for the exact function of ncRNA and ncRNA-mediated regulatory network in cardiomyocyte generation. We will use the in vitro and in vivo model of cardiomyocyte generation, and our expertise in the function and mechanism research of ncRNA in regulating cell fate. In combination with the bioinformatics analysis and systematic screening for cardiomyocyte-specific ncRNA that may potentially target myocardial cell related transcription factors and signaling pathways, we will further clarify the function of specific ncRNA such as lncRNA-TPB in cardiomyocyte generation. The specific regulatory mechanism of ncRNA in cardiomyocyte generation will be further elucidated by molecular experiments including luciferase reporter gene, RNA pull-down, RIP and so on. On this basis, the newly discovered ncRNA will be introduced into the in vivo transdifferentiation model, and the effects of key ncRNA on the efficiency of in vivo transdifferentiation, and cardiac function recovery will also be investigated. The completion of this project will further enrich the ncRNA-mediated epigenetic-specific regulatory network in cardiomyocyte generation, provide important basis for obtaining high quality cardiomyocytes with high efficiency, and potential target for early and safe application of cardiomyocytes in disease treatment.