Single-cell Reconstruction of the Adult Human Heart During Heart Failure and Recovery Reveals the Cellular Landscape Underlying Cardiac Function

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2020 Jan 10

PMID 31915373

Citations 202

Authors

Li Wang

Peng Yu

Bingying Zhou

Jiangping Song

Zheng Li

Mingzhi Zhang

Guangran Guo

Yin Wang

Xiao Chen

Leng Han

Shengshou Hu

Affiliations

Soon will be listed here.

Abstract

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.

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