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Comprehensive Single-Cell Multiomic Profiling of the Human Heart in Health and Disease

We profiled all four chambers (left ventricle, right ventricle, left atrium, right atrium) of human hearts from 36 donors (23 with heart failure, 13 non-failing controls) using single-cell multiome (joint chromatin accessibility and gene expression), Droplet Paired-Tag (joint histone modification H3K27ac/H3K27me3 and gene expression), and Droplet Hi-C (single-cell chromatin conformation) assays. The heart failure cohort included 13 ischemic (ICM) and 10 non-ischemic cardiomyopathy (NICM) patients. Genotyping array and whole genome sequencing (WGS) data were also generated from the same donors (when applicable - not all donors have WGS/Genotyping data). Integrative analyses across 759,222 total nuclei revealed cell type-specific changes in gene regulatory programs, chromatin organization, and transcription factor networks - particularly in cardiomyocytes and fibroblasts - during heart failure. Mapping cell type-specific enhancer-gene interactions enabled identification of likely causal genetic contributors to heart failure from GWAS data. Data include individual-level genotype, phenotype, WGS, single-cell RNA-seq (scRNA-seq), single-cell ATAC-seq (scATAC-seq), single-cell histone modification, and single-cell Hi-C data (scHi-C).