A cross-organ single-cell analysis of hypertension
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.
Authors
- Hong Xue (ORCID: https://orcid.org/0000-0002-8133-9828)
- Mark A. Vanden Avond (ORCID: https://orcid.org/0000-0003-4872-1993)
- Lishu He (ORCID: https://orcid.org/0000-0003-0730-2602)
- Andrew s. Greene
- Maya Guenther
- Michael N. Grzybowski (ORCID: https://orcid.org/0000-0002-8115-2748)
- Aron M. Geurts (ORCID: https://orcid.org/0000-0002-4347-2505)
- Sridhar Rao (ORCID: https://orcid.org/0000-0003-2688-9541)
- Bhavika Therani (ORCID: https://orcid.org/0000-0002-0560-5362)
- Qiongzi Qiu (ORCID: https://orcid.org/0000-0002-6486-6394)
- Kristie Usa (ORCID: https://orcid.org/0009-0000-0083-2091)
- Shima Sadri
- Allen W. Cowley (ORCID: https://orcid.org/0000-0002-0801-6248)
- Mingyu Liang (ORCID: https://orcid.org/0000-0002-6970-989X)
- Jing Liu (ORCID: https://orcid.org/0000-0003-0575-084X)
- Vinod Kumar (ORCID: https://orcid.org/0000-0001-8098-9901)
- Jing Huang (ORCID: https://orcid.org/0000-0002-9607-7250)
- Yong Liu (ORCID: https://orcid.org/0000-0001-8489-1741)
- Rajan Pandey (ORCID: https://orcid.org/0000-0003-2535-3542)
- Pengyuan Liu
Institutions
- University of Arizona (US)
- Medical College of Wisconsin (US)
- Jackson Laboratory (US)
- Versiti Blood Center of Wisconsin (US)
Publication Details
- Journal
- Science
- Published
- 2026-08-13
- DOI
- https://doi.org/10.1126/science.aea6187
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health