心肌细胞（CMs）转分化替代治疗心脏疾病极具前景，但存在转分化CMs成熟度低、功能差、致心律失常等难题。与编码基因相比，非编码RNA（ncRNA）的表达特异性高，可精确调控细胞命运决定，但在CMs成熟中研究极少。我们利用高通量测序筛选并鉴定了若干个与CMs成熟转变相关的ncRNA（lncRNA_CMPR、miR-370-3p等）。本项目将结合CMs成熟调控的已知信号通路、表观蛋白等，利用生物信息分析及分子、细胞生物学表型和功能监测手段，阐明心肌成熟关键ncRNA的作用机制，进一步明确这些ncRNA能否促进转分化CMs成熟。体外研究基础上，将这些ncRNA介入体内CMs转分化治疗小鼠心梗模型中，观察其能否更有效地促进转分化CMs成熟、挽救小鼠心功能和降低致心律失常风险。本项目的研究将有助于理解调控CMs成熟的ncRNA网络，并为实现转分化CMs安全治疗心脏疾病提供理论依据和实验基础。

Cardiomyocyte transdifferentiation provides a promising treatment for heart disease, but the immaturity of transdifferentiated cardiomyocytes potentially results in poor capability and arrhythmia. In comparison with coding genes, non-coding RNA (ncRNA), as the important epigenetic regulator, has the unique expression pattern and powerful regulatory ability to participate cell fate determination, but its role in the regulation of cardiomyocyte maturation is seldom studied. To this end, we have screened and identified several ncRNAs (lncRNA_CMPR; miR-370-3p etc) related to the cardiomyocyte maturation by high-throughput sequencing. Therefore, we intend to study the mode of action and mechanism of key ncRNA based on known pathways and epigenetic proteins associated with cardiomyocyte maturation or by using bioinformatic analysis, molecular or cell biological approach and so on. And to further clarify whether these ncRNAs can improve the maturation of transdifferentiated cardiomyocytes. On this basis, we plan to establish an animal model of cardiomyocyte transdifferentiation in vivo for the treatment of myocardial infarction (MI), and to investigate whether intervention of these ncRNAs could more effectively rescue the heart function and reduce the risk of arrhythmia in MI mice. The research of this project will help to understand the regulatory network of ncRNA involved in cardiomyocyte maturation, and provide more theoretical and experimental basis for the future use of these ncRNA as target for the safe cardiomyocyte transdifferentiation in the treatment of heart disease.