Key result
Multiomic analysis reveals dynamic changes in cell composition and gene-regulatory programs in heart failure.
Why the study?
Heart failure is a leading cause of morbidity and mortality, but the gene-regulatory mechanisms driving cell type-specific pathologic responses remain undefined.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This study provides a roadmap to the landscape of major cardiac cell types of all four chambers of the normal and failing human heart. These findings establish a mechanistic framework for biological pathways of heart failure development and present multiple targets for developing new therapies for heart failure.”
“By connecting genetic risk, gene regulation and cell-specific disease processes, this study provides a blueprint for precision therapies in heart failure. It opens the door to targeting the right mechanisms in the right cells at the right time.”
“It is incredibly exciting and rewarding to see that this research has led to discoveries that are now leading to new therapies for patients with heart failure—fulfilling the hopes and expectations of both the patients who so generously contributed to this research and all of us who have worked to turn their gift into better treatments for our patients.”
This study provides multimodal gene-regulatory maps of the human heart, offering a framework for designing precise, cell type-targeted therapies for heart failure.
Heart failure is a leading cause of morbidity and mortality, yet gene-regulatory mechanisms driving cell type-specific pathologic responses remain undefined. Here, we present the cell type-resolved transcriptomes, chromatin accessibility, histone modifications, and chromatin organization of 13 nonfailing and 23 failing human hearts across all cardiac chambers. Integrative analyses revealed dynamic changes in cell type composition, gene-regulatory programs, and chromatin organization, particularly in cardiomyocytes and fibroblasts. Mapping cell type-specific enhancer-gene interactions from these analyses enabled the illumination of likely causal genetic contributors to heart failure from genetic association data. Together, these findings provide multimodal gene-regulatory maps of the human heart in health and disease, offering a framework for designing precise, cell type-targeted therapies for treating heart failure.
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Xie et al. (2026) studied Heart failure (n=36). Heart failure vs. Nonfailing hearts was evaluated on Cell type-resolved transcriptomes, chromatin accessibility, histone modifications, and chromatin organization. Multiomic analysis of 23 failing and 13 nonfailing human hearts revealed dynamic changes in cell type composition, gene-regulatory programs, and chromatin organization in heart failure.
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