A cross-organ single-cell analysis of hypertension.

Document Type

Article

Publication Date

8-13-2026

Keywords

JMG, Animals, Humans, Male, Mice, Rats, Angiotensin II, Blood Pressure, Hypertension, Muscle, Smooth, Vascular, Rats, Inbred Dahl, Rats, Inbred SHR, Single-Cell Gene Expression Analysis, Mice, Inbred C57BL, Kidney Tubules, Organ Specificity

JAX Source

Science. 2026 Aug 13;393(6812):eaea6187.

ISSN

1095-9203

PMID

42594205

DOI

https://doi.org/10.1126/science.aea6187

Abstract

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.

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