Evidence map›Paper›PMID 38152886›Full record

SynthesisArteriosclerosis, thrombosis, and vascular biology2024

Comprehensive Integration of Multiple Single-Cell Transcriptomic Data Sets Defines Distinct Cell Populations and Their Phenotypic Changes in Murine Atherosclerosis.

Disha Sharma, Matthew D Worssam, Albert J Pedroza, Alex R Dalal, Haizea Alemany, Hyun-Jung Kim, Ramendra Kundu, Michael P Fischbein, Paul Cheng, Robert Wirka and 1 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  2. Article
  3. PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Disha SharmaDivision of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0001-9486-2709
Matthew D WorssamDivision of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0003-4391-5377
Albert J PedrozaDivision of Cardiothoracic Surgery (A.J.P., A.R.D., M.P.F.), Stanford University School of Medicine, CA.
Alex R DalalDivision of Cardiothoracic Surgery (A.J.P., A.R.D., M.P.F.), Stanford University School of Medicine, CA.ORCID 0000-0002-9993-3817
Haizea AlemanyDivision of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.
Hyun-Jung KimDivision of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0001-6264-0220
Ramendra KunduDivision of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0001-9618-2600
Michael P FischbeinDivision of Cardiothoracic Surgery (A.J.P., A.R.D., M.P.F.), Stanford University School of Medicine, CA.ORCID 0000-0002-0638-2025
Paul Cheng *Division of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0003-3429-2702
Robert Wirka *Division of Cardiology, McAllister Heart Institute, UNC School of Medicine, Chapel Hill, NC (R.W.).ORCID 0000-0001-9131-9508
Thomas Quertermous *Division of Cardiovascular Medicine (D.S., M.D.W., H.A., H.-J.K., R.K., P.C., T.Q.), Stanford University School of Medicine, CA.ORCID 0000-0002-7645-9067
Stanford University · USUniversity of North Carolina Health Care · US

Funding

Stanford Center for Connecting DNA Variants to Function and PhenotypeUM1HG011972 · NHGRI · STANFORD UNIVERSITY · PI JESSE M ENGREITZ, THOMAS QUERTERMOUS · 2021 to 2026
$10.5M
T32 Training Program in Mechanisms and Innovation in Vascular DiseaseT32HL098049 · NHLBI · STANFORD UNIVERSITY · PI Nicholas James Leeper, Philip S Tsao · 2010 to 2026
$6.3M
Causal variant association mechanisms in TCF21 binding coronary disease lociR01HL134817 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2017 to 2026
$6.2M
Mechanism of the Coronary Heart Disease Association at Chromosome 6q23.2R01HL109512 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2011 to 2019
$6.1M
The SMAD3 signaling network in coronary artery disease riskR01HL139478 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2018 to 2026
$3.7M
PDGFD regulates a transcriptional network to modulate smooth muscle cell transition and coronary artery disease riskR01HL156846 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
Identifying tobacco-genetic interactions through study of the aryl hydrocarbon receptor pathway.R01HL151535 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2021 to 2024
$2.7M
Molecular mechanisms of vascular calcification and their connection to coronary disease riskR01HL158525 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2022 to 2025
$2.4M
Gene regulatory networks controlling smooth muscle phenotype and vasculardisease riskR01HL171045 · NHLBI · STANFORD UNIVERSITY · PI THOMAS QUERTERMOUS · 2024 to 2026
$2.1M
LncRNA Transcriptional Mechanisms of Coronary Artery Disease RiskR01HL145708 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2019 to 2022
$1.6M
Identification of causal coronary heart disease variation in smooth muscle cellsR33HL120757 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS · 2016 to 2018
$1.6M
From Locus to Function: Role of ZEB2 in Human Risk of Coronary Artery DiseaseK08HL153798 · NHLBI · STANFORD UNIVERSITY · PI CHENG, PAUL PO SHENG · 2020 to 2024
$933k
NHGRI NIH HHS UM1 HG011972NHLBI NIH HHS F32 HL143847NHLBI NIH HHS K08 HL152308NHLBI NIH HHS K08 HL153798NHLBI NIH HHS R01 HL109512NHLBI NIH HHS R01 HL134817NHLBI NIH HHS R01 HL139478NHLBI NIH HHS R01 HL145708NHLBI NIH HHS R01 HL151535NHLBI NIH HHS R01 HL156846NHLBI NIH HHS R01 HL158525NHLBI NIH HHS R01 HL171045NHLBI NIH HHS R21 HL120757NHLBI NIH HHS R33 HL120757NHLBI NIH HHS T32 HL098049
6 · The paper itself

Abstract

backgroundThe application of single-cell transcriptomic (single-cell RNA sequencing) analysis to the study of atherosclerosis has provided unique insights into the molecular and genetic mechanisms that mediate disease risk and pathophysiology. However, nonstandardized methodologies and relatively high costs associated with the technique have limited the size and replication of existing data sets and created disparate or contradictory findings that have fostered misunderstanding and controversy.

methodsTo address these uncertainties, we have performed a conservative integration of multiple published single-cell RNA sequencing data sets into a single meta-analysis, performed extended analysis of native resident vascular cells, and used in situ hybridization to map the disease anatomic location of the identified cluster cells. To investigate the transdifferentiation of smooth muscle cells to macrophage phenotype, we have developed a classifying algorithm based on the quantification of reporter transgene expression.

resultsThe reporter gene expression tool indicates that within the experimental limits of the examined studies, transdifferentiation of smooth muscle cell to the macrophage lineage is extremely rare. Validated transition smooth muscle cell phenotypes were defined by clustering, and the location of these cells was mapped to lesion anatomy with in situ hybridization. We have also characterized 5 endothelial cell phenotypes and linked these cellular species to different vascular structures and functions. Finally, we have identified a transcriptomically unique cellular phenotype that constitutes the aortic valve.

conclusionsTaken together, these analyses resolve a number of outstanding issues related to differing results reported with vascular disease single-cell RNA sequencing studies, and significantly extend our understanding of the role of resident vascular cells in anatomy and disease.

Indexed as

AtherosclerosisGene Expression ProfilingAnimalsMacrophagesMiceMyocytes, Smooth MusclePhenotypeTranscriptomealgorithmsaortic valvediseasegene expressionphenotype

Identifiers

PMID38152886
PMCPMC11285358
OpenAlexW4390340990

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.