A cross-organ single-cell analysis of hypertension
Qiongzi Qiu, Yong Liu, Hong Xue, Rajan Pandey, Jing Liu, Lishu He, Pengyuan Liu, Bhavika Therani, Vinod Kumar, Jing Huang, Shima Sadri, Maya Guenther, Kristie Usa, Michael Grzybowski, Mark A. Vanden Avond, Andrew S. Greene, Allen W. Cowley, Sridhar Rao, Aron M. Geurts, Mingyu LiangHypertension 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.