A cross-organ single-cell analysis of hypertension

• 成果类型: Article
• 署名作者: Qiu, Qiongzi; Liu, Yong; Xue, Hong; Pandey, Rajan; Liu, Jing; He, Lishu; Liu, Pengyuan; Therani, Bhavika; Kumar, Vinod; Huang, Jing; Sadri, Shima; Guenther, Maya; Usa, Kristie; Grzybowski, Michael; Vanden Avond, Mark A.; Greene, Andrew S.; Cowley, Allen W.; Rao, Sridhar; Geurts, Aron M.; Liang, Mingyu
• 署名单位: University of Arizona; University of Arizona Health Sciences; University of Arizona Health Sciences; University of Arizona; Medical College of Wisconsin; Jackson Laboratory; Medical College of Wisconsin; Medical College of Wisconsin
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aea6187
• 发表日期: 2026-08-13
• 页码: eaea6187
• 关键词: genome-wide association; CORONARY-ARTERY-DISEASE; BLOOD-PRESSURE REGULATION; GENETIC RISK-FACTORS; kidney-function; susceptibility locus; ischemic-stroke; IDENTIFIES 8; RESISTANT HYPERTENSION; insulin-resistance

摘要

Hypertension is a leading cause of disease burden and mortality. Here, we present a single-cell analysis of hypertension and end-organ damage across six organs and tissues in angiotensin II-treated mice, Dahl salt-sensitive rats, and spontaneously hypertensive rats. We identified gene programs associated with blood pressure and renal injury, including a conserved vascular smooth muscle cell program and cross-segment renal tubular programs, along with tissue-specialized endothelial adaptations and coordinated changes across cell types in select organs. Integration with human genomic data revealed model-specific and shared cell type-trait links. We prioritized a noncoding variant (rs28451064) and used genome editing to demonstrate its in vivo effect on blood pressure and allele-specific regulation of local genes. Our study provides a multimodel, cross-organ cellular resource for hypertension research.