Single-cell multiomics and chromatin structure reveal gene-regulatory dynamics in heart failure

• 成果类型: Article
• 署名作者: Xie, Yang; Tucciarone, Luca; Farah, Elie N.; Chang, Lei; Yang, Qian; Shankar, Thirupura S.; Elison, Weston; Tran, Shaina; Djulamsah, Jovina; Lie, Audrey; Loe, Timothy; Holman, Alyssa R.; Corban, Sierra; Buchanan, Justin; Mamde, Sainath; Zhou, Haowen; Elgamal, Ruth M.; Tseliou, Eleni; Huang, Vincent; Wang, Zhaoning; Chiu, Jeffrey Huey-Chuan; Melton, Rebecca; Griffin, Emily; Zhang, Qingquan; Lucero, Jacinta; Navankasattusas, Sutip; Li, Daofeng; Seng, Chanrung; Destici, Eugin; Selzman, Craig H.; D'Antonio-Chronowska, Agnieszka; Wang, Ting; Wang, Allen; Drakos, Stavros G.; Gaulton, Kyle J.; Ren, Bing; Chi, Neil C.
• 署名单位: University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Utah System of Higher Education; University of Utah; University of California System; University of California San Diego; University of California System; University of California San Diego; Utah System of Higher Education; University of Utah; Columbia University; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital; Washington University (WUSTL); Utah System of Higher Education; University of Utah; Washington University (WUSTL); University of California System; University of California San Diego; University of California System; University of California San Diego; Columbia University; Cornell University; Weill Cornell Medicine; NewYork-Presbyterian Hospital; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady6893
• 发表日期: 2026-07-23
• 页码: eady6893
• 关键词: genome-wide association; transcription; expression; insights; etiology

摘要

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.