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Cellular senescence
Research brief

Single-cell multiomic QTL mapping in proliferating and senescent HUVECs from 100 donors

In primary HUVECs from 100 genotyped donors, the authors compared proliferating and replicatively senescent cells using single-cell multiome ATAC-RNA profiles and joint chromatin-accessibility/expression QTL mapping; they report associations missed by single-modality scans and a candidate variant, rs2019090, linked to PDGFD regulation. [1]

Automatic summary · not editorially reviewed

The key findings

  1. The study used single-cell multiome ATAC-RNA profiles from proliferating and replicatively senescent primary HUVECs derived from 100 genotyped donors. [1]

  2. Joint chromatin accessibility-expression QTL mapping recovered associations missed by single-modality scans and prioritized candidate variants and effector genes at cardiovascular loci. [1]

  3. rs2019090 was reported to modulate PDGFD expression and endothelial phenotypes through senescence-amplified, allele-specific, HMGA1-associated enhancer-promoter regulation. [1]

The source at a glance

Study type / format
Laboratory single-cell multiomic QTL mapping study (abstract)
Population / context
Primary human umbilical vein endothelial cells (HUVECs) from 100 genotyped donors, studied in proliferating and replicatively senescent states.
Summary based on
Study abstract
Publication status
Preprint · peer-review status not confirmed
Original publication
September 21, 2026

HUVECs from 100 donors, proliferating versus senescent

The abstract describes single-cell multiome ATAC-RNA profiles from primary human umbilical vein endothelial cells (HUVECs) derived from 100 genotyped donors. Cells were studied in two states: proliferating and replicatively senescent. The authors frame the question as how cellular senescence reshapes inherited regulatory effects across chromatin and transcription and how this may relate to non-coding risk loci of complex diseases.

Supporting source [1]

Joint accessibility-expression mapping found missed associations

Alongside state-resolved expression QTL and chromatin-accessibility QTL mapping, the authors applied covariance-aware multivariate QTL mapping to identify chromatin accessibility-expression QTLs (caeQTLs), treating accessibility and expression as a joint phenotype. The joint analysis recovered moderate, asymmetric and modality-distributed associations that single-modality scans missed, revealed senescence-associated regulatory programs and prioritized candidate causal variants and effector genes at cardiovascular loci. Fine-mapping, chromatin-state annotation, heritability enrichment and independent SNP-to-gene algorithms were described as convergent orthogonal support.

Supporting source [1]

rs2019090 and PDGFD in senescence-amplified regulation

The mechanistic part of the abstract reports that rs2019090 modulates PDGFD expression and endothelial phenotypes through senescence-amplified, allele-specific, HMGA1-associated enhancer-promoter regulation. The authors conclude that senescence-resolved joint multiomic QTL mapping is a framework for narrowing the missing regulation gap in complex disease genetics. This is a proposed framework, not a validated clinical tool.

Supporting source [1]

How to interpret this

This is an abstract only; the full text was not reviewed. The work is a laboratory study in primary HUVECs from 100 donors, not a human clinical trial, and the reported associations and mechanistic findings are not established causes of disease or clinical benefits. The framework is proposed, not validated.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
Single-cell multiomic QTL mapping reveals state-dependent genetic regulation and associated gene during cellular senescence

Yi X, Wang X, Liu K, Zhao L, Chen F, Jian Q, Wang J, Lu H, Dong W, Zhou Y, Chang Y, Gu X, Sham PC, Huang D, Li MJ. · europepmc.org · September 21, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    from proliferating and replicatively senescent primary HUVECs
  2. Finding 2 ↑

    associations missed by single-modality scans
  3. Finding 3 ↑

    rs2019090 modulates PDGFD expression and endothelial phenotypes

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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