A cross-organ single-cell analysis of hypertension

Q: What is the clinical evidence from this study?

Population: Hypertension. Intervention: Hypertension models (angiotensin II, Dahl salt-sensitive, spontaneously hypertensive). Primary outcome: Gene programs associated with blood pressure and renal injury.

Q: What does this research mean for the field?

Hypertension involves conserved cross-organ vascular smooth muscle and renal tubular gene programs, along with functional noncoding genetic variants such as rs28451064 that regulate local gene expression to influence blood pressure in vivo. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

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 Liang

doi:10.1126/science.aea6187

Key result

Single-cell analysis in hypertensive models identifies conserved gene programs and a noncoding variant affecting BP.

Why the study?

Hypertension is a leading cause of disease burden and mortality, motivating a comprehensive cellular analysis across multiple organs and models.

Key Points

To characterize cell-type-specific transcriptional changes across multiple organs in rodent models of hypertension and connect them with human genetic risk factors.
Performed single-cell transcriptomic profiling across six organs and tissues in angiotensin II–treated mice, Dahl salt–sensitive rats, and spontaneously hypertensive rats.
Integrated single-cell expression profiles with human genomic data and evaluated the functional effect of candidate noncoding variant rs28451064 using in vivo genome editing.
Identified conserved vascular smooth muscle cell and cross-segment renal tubular gene programs associated with elevated blood pressure and renal injury across models.
Observed tissue-specialized endothelial adaptations and coordinated multi-lineage cellular responses in select organs.
Demonstrated that the noncoding variant rs28451064 modulates blood pressure in vivo through allele-specific regulation of local target genes.

Structured PICO

P

Population

angiotensin II–treated mice, Dahl salt–sensitive rats, and spontaneously hypertensive rats

E

Exposure

single-cell analysis across six organs and tissues, integration with human genomic data, and genome editing of noncoding variant rs28451064

O

Outcome

gene programs associated with blood pressure and renal injury, and in vivo effect of noncoding variant on blood pressuresurrogate

This study provides a comprehensive single-cell transcriptomic resource across multiple organs and animal models of hypertension, identifying key gene programs and validating a noncoding variant's effect on blood pressure.

Implication

These animal findings should not change practice; leaves open their use to prioritize human hypertension targets.

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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Qiu et al. (2026) studied Hypertension. Hypertension models (angiotensin II, Dahl salt-sensitive, spontaneously hypertensive) was evaluated on Gene programs associated with blood pressure and renal injury. Single-cell analysis across six organs in hypertensive animal models identified conserved vascular and renal gene programs, and prioritized a noncoding variant (rs28451064) affecting blood pressure.

synapsesocial.com/papers/6a801a2875c2e31742c86afb https://doi.org/10.1126/science.aea6187

View at Publisher

Ask AI

Bookmark

Share

A cross-organ single-cell analysis of hypertension

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

A cross-organ single-cell analysis of hypertension

Key Points

Structured PICO

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading