Abstract
Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.
Highlights
Cardiovascular disease is the leading cause of death worldwide
Haemodynamics changes in the postnatal period and the distinct gene regulatory networks that operate in each heart field presumably prime gene expression patterns of adult heart cells[1]
By combining single-cell and single-nuclear RNA-seq data with machine learning and in situ imaging techniques, we provide detailed insights across the repertoire of cardiac cells, including cardiomyocytes and endothelial cells (ECs)
Summary
Our analyses of approximately half a million single cells and nuclei from six distinct cardiac regions from fourteen donors considerably expand an emerging reference adult heart cell atlas. 3. Wang, L. et al Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. M. Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. X. et al Single-cell RNA-Seq of the developing cardiac outflow tract reveals convergent development of the vascular smooth muscle cells. J. et al Genetic fate mapping defines the vascular potential of endocardial cells in the adult heart. Q. et al Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. J.-M. et al Regulator of G-protein signaling 5 prevents smooth muscle cell proliferation and attenuates neointima formation. Y. et al Hyaluronan receptor LYVE-1-expressing macrophages maintain arterial tone through hyaluronan-mediated regulation of smooth muscle cell collagen. M. et al Population and single-cell analysis of human cardiogenesis reveals unique LGR5 ventricular progenitors in embryonic outflow tract. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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