Owing to the prevalence and high mortality rates of cardiac diseases, a more detailed characterization of the human heart is necessary; however, this has been largely impeded by the cellular diversity of cardiac tissue and limited access to samples. Here, we show transcriptome profiling of 21,422 single cells—including cardiomyocytes (CMs) and non-CMs (NCMs)—from normal, failed and partially recovered (left ventricular assist device treatment) adult human hearts. Comparative analysis of atrial and ventricular cells revealed pronounced inter- and intracompartmental CM heterogeneity as well as compartment-specific utilization of NCM cell types as major cell-communication hubs. Systematic analysis of cellular compositions and cell–cell interaction networks showed that CM contractility and metabolism are the most prominent aspects that are correlated with changes in heart function. We also uncovered active engagement of NCMs in regulating the behaviour of CMs, exemplified by ACKR1⁺-endothelial cells, injection of which preserved cardiac function after injury. Beyond serving as a rich resource, our study provides insights into cell-type-targeted intervention of heart diseases.

由于心脏病的流行和高死亡率，有必要对人类心脏进行更详细的描述；然而，这在很大程度上受到心脏组织细胞多样性和样本获取有限的阻碍。在这里，我们展示了来自正常、失败和部分恢复（左心室辅助装置治疗）成人心脏的 21,422 个单细胞（包括心肌细胞 (CM) 和非 CM (NCM)）的转录组分析。心房和心室细胞的比较分析揭示了明显的隔间和隔间内 CM 异质性以及 NCM 细胞类型作为主要细胞通讯枢纽的隔间特异性利用。对细胞组成和细胞间相互作用网络的系统分析表明，CM 收缩性和新陈代谢是与心脏功能变化相关的最突出的方面。我们还发现 NCM 积极参与调节 CM 的行为，例如 ACKR1⁺ -内皮细胞，注射后可保留损伤后的心脏功能。除了作为丰富的资源之外，我们的研究还提供了对心脏病的细胞类型靶向干预的见解。