An integrated cell atlas of 2.4 million cardiac cells across 209 individuals in health and disease

Cardiovascular disease remains the leading cause of global mortality. Understanding its complexity requires dissecting the heartʼs cellular landscape. Here we present HeartMap, a comprehensive single-nucleus RNA sequencing atlas of the adult human heart. This resource integrates data from nine studies, encompassing over 2.4 million nuclei, 209 individuals, eight anatomical regions and seven disease and healthy states. After rigorous data harmonization and method comparison of batch correction methods, we characterized transcriptional diversity across 14 cell types. To demonstrate the utility of HeartMap, we identified robust disease-associated gene signatures in dilated cardiomyopathy by comparing multiple studies. Notably, we identified distinct activated fibroblast populations, enriched for COL22A1 or TNC, that display variable prevalence across cardiomyopathies. HeartMap provides a valuable tool for exploring cardiac disease at the single-cell level, facilitating both fundamental research and potential therapeutic development. Datar et al. integrate multiple single-nucleus RNA sequencing datasets to generate a unified atlas of cardiovascular diseases, including ischemic and non-ischemic cardiomyopathies, myocardial infarction and coronary artery disease, and highlight the differential activation of fibroblast subsets across conditions.