An Integrated Cell Atlas of 2.4 million cells across 209 Individuals in Health and Disease

Yesh Datar1,2, Mark Chaffin1, Bridget Simonson1, Alex Mandia1, Patrick T. Ellinor1,3,4

1.      Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA

2.      Boston University Chobanian and Avedesian School of Medicine, Boston, MA USA

3.      Cardiology Division, Mass General Brigham, Boston, MA, USA

4.      Heart and Vascular Institute, Mass General Brigham, Boston, MA, USA

Cardiovascular disease remains the leading cause of global mortality. Understanding its complexity requires dissecting the heart's 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 harmonisation and method comparison of batch-correction methods, we characterised 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.