Evidence map›Paper›PMID 32962412›Full record

ArticleCirculation2020

Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human.

Huize Pan, Chenyi Xue, Benjamin J Auerbach, Jiaxin Fan, Alexander C Bashore, Jian Cui, Dina Y Yang, Sarah B Trignano, Wen Liu, Jianting Shi and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 431 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
431citing papers in PubMed, 1 pooled it
25.4field-weighted citation impact, top 1% 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

431 citing papers in PubMed, 1 synthesis or guideline pooled it, 589 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  5. PET imaging of atherosclerotic plaques using the stabilin-2-targeted tracerEuropean journal of nuclear medicine and molecular imaging · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026
    Review
  16. Review
  17. Review
  18. Decoding the Sex-Specific Architecture of Carotid Plaque Instability.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  19. Article
  20. Review

371 more citing papers are in PubMed but not listed here.

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

22 authors at 4 institutions in 1 country.

Huize Pan *Division of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Chenyi Xue *Division of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Benjamin J Auerbach *Graduate Group in Genomics and Computational Biology (B.J.A.), University of Pennsylvania, Philadelphia.
Jiaxin FanDepartment of Biostatistics, Epidemiology, and Informatics (J.F., M.L.), University of Pennsylvania, Philadelphia.
Alexander C BashoreDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Jian CuiDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Dina Y YangDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Sarah B TrignanoDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Wen LiuDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Jianting ShiDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Chinyere O IhuegbuDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Erin C BushDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Jeremy WorleyDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Lukas VlahosDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Pasquale LaiseDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Robert A SolomonDepartment of Neurologic Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center (R.A.S., E.S.C.).
Edward S ConnollyDepartment of Neurologic Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center (R.A.S., E.S.C.).
Andrea CalifanoDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Peter A SimsDepartment of Systems Biology (E.C.B., J.W., L.V., P.L. A.C., P.A.S.), Columbia University Irving Medical Center, New York.
Hanrui ZhangDivision of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Mingyao Li *Department of Biostatistics, Epidemiology, and Informatics (J.F., M.L.), University of Pennsylvania, Philadelphia.
Muredach P Reilly *Division of Cardiology, Department of Medicine (H.P., C.X., A.C.B., J.C., D.Y.Y., S.B.T., W.L., J.S., C.O.I., H.Z., M.P.R.), Columbia University Irving Medical Center, New York.
Columbia University Irving Medical Center · USNewYork–Presbyterian Hospital · USUniversity of Pennsylvania · USJoint Center for Structural Genomics · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Training Program in Computational GenomicsT32HG000046 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI JUNHYONG KIM, Mingyao Li · 1999 to 2026
$9.5M
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic DiseaseR01HL113147 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, REILLY, MUREDACH P · 2012 to 2022
$6.8M
Computational and functional strategies to decipher lncRNAs in human atherosclerosisR01HL150359 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LI, MINGYAO, REILLY, MUREDACH P · 2020 to 2023
$2.7M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
Statistical Methods for Single-Cell TranscriptomicsR01GM125301 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, ZHANG, NANCY R · 2017 to 2020
$1.5M
Mentored Patient Oriented Research in Cardiometabolic DiseaseK24HL107643 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2020
$1.4M
Macrophage-specific function of GWAS CAD-associated LIPA alleles in atherosclerosisR00HL130574 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, HANRUI · 2018 to 2020
$733k
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
NCATS NIH HHS UL1 TR001873NCI NIH HHS P30 CA013696NCI NIH HHS R35 CA197745NHGRI NIH HHS T32 HG000046NHLBI NIH HHS K24 HL107643NHLBI NIH HHS R00 HL130574NHLBI NIH HHS R01 HL113147NHLBI NIH HHS R01 HL150359NIGMS NIH HHS R01 GM125301NIH HHS S10 OD012351NIH HHS S10 OD020056NIH HHS S10 OD021764
6 · The paper itself

Abstract

backgroundSmooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive.

methodsTo reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro.

resultsWe found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed "SEM" cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability.

conclusionsIntegration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.

Indexed as

PhenotypeAnimalsAtherosclerosisCell DedifferentiationCell DifferentiationCell MovementCells, CulturedCell TransdifferentiationFemaleGenetic TherapyGenomicsHumansMaleMiceMice, Inbred C57BLMice, Knockoutatherosclerosiscardiovascular diseaseretinoic acid signalingsingle-cell RNA sequencingsmooth muscle cell

Identifiers

PMID32962412
PMCPMC8104264
OpenAlexW3088819072

What OpenQuestion holds

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Registered trials

None linked

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.