Data from: Single-cell Transcriptome and Epigenomic Reprogramming of Cardiomyocyte-Derived Cardiac Progenitor Cells

The molecular basis underlying spontaneous dedifferentiation and cell cycle reentry of mammalian adult cardiomyocytes (ACMs) during cardiac tissue regeneration is poorly understood. We present data integrating single-cell transcriptome and whole-genome DNA methylome analyses of mouse ACMs to better understand the epigenomic signatures governing their intrinsic cellular plasticity. Compared to parental cardiomyocytes, dedifferentiated myocyte-derived cardiac progenitor-like cells (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlating well with the methylome, our transcriptomic array data derived from single-cell microfluidics show that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. This dataset suggests that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. Understanding how to reprogram cardiomyocyte epigenomic signatures may enable the design of future clinical therapies that induce cardiac regeneration, and prevent heart failure.

哺乳动物成体心肌细胞（adult cardiomyocytes, ACMs）在心脏组织再生过程中自发去分化及细胞周期重进入的分子机制，迄今尚未得到充分阐释。本研究整合小鼠成体心肌细胞的单细胞转录组与全基因组DNA甲基化组分析数据，以深入解析调控其固有细胞可塑性的表观基因组特征。与亲本心肌细胞相比，去分化肌细胞来源的心脏祖细胞样细胞（myocyte-derived cardiac progenitor-like cells, mCPCs）在全基因组范围内呈现出广泛的表观基因组重编程，存在大量差异甲基化区域，涵盖高甲基化与低甲基化两种类型。与甲基化组数据高度吻合的是，本研究基于单细胞微流控技术获得的转录组芯片数据显示：在mCPCs中，编码心脏结构与功能蛋白的基因表达显著下调，而与细胞周期、增殖及干细胞特性相关的基因则显著上调。本数据集表明，哺乳动物心肌细胞的细胞可塑性是协同有序的表观基因组重编程与后续全局性转录组改变共同作用的结果。阐明如何重编程心肌细胞的表观基因组特征，有望为未来开发诱导心脏再生、预防心力衰竭的临床治疗策略提供理论依据。