内源性心肌再生是防治心梗后心衰十分有前景的新策略，但目前存在再生效能低以及临床转化困难等问题，究其可能原因是单纯调控细胞周期未协同调控细胞代谢，导致细胞周期进程难以持续。细胞周期与代谢存在交叉对话且调控交叉对话是实现细胞高效增殖的有效途径。目前心肌细胞是否存在“细胞周期-代谢”交叉对话及其能否成为促心肌再生新策略尚不清楚。我们前期研究发现心肌细胞存在“细胞周期-代谢”交叉对话并筛选出潜在调控交叉对话的环状RNA (circReps1)。因此我们假设：circReps1通过“细胞周期-代谢”交叉对话介导心肌再生。本项目拟采用测序、功能获得/缺失、免疫荧光及遗传谱系追踪等方法：A.验证筛选出潜在调控心肌细胞“细胞周期-代谢”交叉对话的circReps1能高效介导心肌再生；B. 阐明circReps1调控交叉对话介导心肌再生的具体机制。该项目将为今后临床促进心肌再生提供更加高效和精准的新策略。

Endogenous myocardial regeneration is a promising new strategy for prevention and treatment of heart failure after myocardial infarction. However, problems exist such as low regeneration efficiency and clinical transformation difficulty. The possible reason is that these strategies simply regulate cell cycle and ignore to regulate cell metabolism, resulting in unsustained cell cycle progression. Previous studies report that there is a cross-talk between cell cycle and metabolism, and that regulation of this cross-talk presents as an effective way to achieve efficient cell proliferation. However, whether there is a "cell cycle-metabolism" cross-talk in cardiomyocytes is unclear, so is whether regulating the "cell cycle-metabolism" cross-talk can become a new strategy for promoting myocardial regeneration. Our previous study found that there existed "cell cycle-metabolism" cross-talk in cardiomyocytes, and we screened a new circRNA Reps1 which potentially regulates "cell cycle-metabolism" cross-talk in cardiomyocytes. Therefore, we hypothesize that circReps1 regenerates myocardial regeneration through a "cell cycle-metabolism" cross-talk. In this study, we aim to use the methods of sequencing, the gain- and loss-of-function, immunofluorescence and other methods to explore whether circReps1 could promote cardiac proliferation efficiently both in vivo and in vitro. In addition, we will explore the mechanism of how circReps1 regulates the "cell cycle-metabolism" cross-talk. The project may provide a more efficient and accurate new strategy for clinical prevention and treatment of heart failure after myocardial infarction in the future.