Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function
Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function
复制标题
心力衰竭和恢复期间成人心脏的单细胞重建揭示了心脏功能背后的细胞景观
DOI：
10.1038/s41556-019-0446-7
复制
发表时间：
2020-01-01
影响因子：
21.3
通讯作者：
Hu, Shengshou
中科院分区：
文献类型：
--
作者：
Wang, Li;Yu, Peng;Hu, Shengshou
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的限制。在这里，我们展示了来自正常、衰竭和部分恢复（左心室辅助装置治疗）的成年人心脏的21,422个单细胞（包括心肌细胞（CMs）和非心肌细胞（ncm））的转录组分析。心房细胞和心室细胞的比较分析揭示了明显的室间和室内CM异质性，以及NCM细胞类型作为主要细胞通信枢纽的室特异性利用。对细胞组成和细胞-细胞相互作用网络的系统分析表明，心肌收缩性和代谢是与心功能变化相关的最突出方面。我们还发现ncm积极参与调节CMs的行为，ACKR1+内皮细胞就是一个例子，注射ACKR1+内皮细胞可以保护损伤后的心脏功能。除了提供丰富的资源外，我们的研究还为心脏疾病的细胞类型靶向干预提供了见解。
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.