Cells of the adult human heart

TLDR

Cardiovascular disease is the leading cause of death worldwide, and understanding the complete repertoire of cardiac cell types and their gene expression profiles is essential for elucidating the molecular mechanisms underlying heart health and disease. The study aims to characterize six anatomical regions of the adult human heart using large‑scale single‑cell and single‑nucleus transcriptomic analyses. The authors employed large‑scale single‑cell and single‑nucleus transcriptomic analyses to map cellular composition across six adult heart regions. The resulting cardiac cell atlas reveals extensive heterogeneity among cardiomyocytes, pericytes, fibroblasts, and immune cells, identifies distinct atrial versus ventricular subsets and arterio‑venous vascular gradients, and maps macrophage‑fibroblast‑cardiomyocyte interaction networks, thereby providing a comprehensive reference for future heart research.

Abstract

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.