Evidence map›Paper›PMID 32972203›Full record

ArticleCirculation2020

Single-Cell RNA Sequencing Analysis Reveals a Crucial Role for CTHRC1 (Collagen Triple Helix Repeat Containing 1) Cardiac Fibroblasts After Myocardial Infarction.

Adrián Ruiz-Villalba, Juan P Romero, Silvia C Hernández, Amaia Vilas-Zornoza, Nikolaus Fortelny, Laura Castro-Labrador, Patxi San Martin-Uriz, Erika Lorenzo-Vivas, Paula García-Olloqui, Marcel Palacio and 21 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
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 170 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed, 2 pooled it
23.2field-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

170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 255 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. An NFATC4 phospho-switch links matrix stiffness to fibroblast fate.The Journal of clinical investigation · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

110 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

31 authors at 8 institutions in 4 countries.

Adrián Ruiz-Villalba *Program of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Juan P Romero *Advanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Silvia C Hernández *Program of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Amaia Vilas-ZornozaAdvanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Nikolaus FortelnyCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (N.F., C.B.).
Laura Castro-LabradorAdvanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Patxi San Martin-UrizAdvanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Erika Lorenzo-VivasAdvanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Paula García-OlloquiProgram of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Marcel PalacioDepartment of Cardiology (M.P., J.J.G.), Clínica Universidad de Navarra, Pamplona, Spain.
Juan José GaviraDepartment of Cardiology (M.P., J.J.G.), Clínica Universidad de Navarra, Pamplona, Spain.
Gorka BastarrikaDepartment of Radiology (G.B.), Clínica Universidad de Navarra, Pamplona, Spain.
Stefan JanssensDepartment of Cardiovascular Sciences, Clinical Cardiology, KU Leuven, Belgium (S.J., M.W.).
Ming WuDepartment of Cardiovascular Sciences, Clinical Cardiology, KU Leuven, Belgium (S.J., M.W.).
Elena IglesiasProgram of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Gloria AbizandaProgram of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Xabier Martinez de MorentinTranslational Bioinformatics Unit (TransBio), NavarraBiomed, Pamplona, Spain (X.M.d.M., M.L., N.P., D.G.-C.).
Miren LasagaTranslational Bioinformatics Unit (TransBio), NavarraBiomed, Pamplona, Spain (X.M.d.M., M.L., N.P., D.G.-C.).
Nuria PlanellTranslational Bioinformatics Unit (TransBio), NavarraBiomed, Pamplona, Spain (X.M.d.M., M.L., N.P., D.G.-C.).
Christoph BockCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (N.F., C.B.).
Diego AlignaniFlow Cytometry Unit (D.A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Gema MedalProgram of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Igor PrudovskyMaine Medical Center Research Institute, Scarborough (I.P., Y.-R.J., S.R., H.Y., V.L.).
Yong-Ri JinMaine Medical Center Research Institute, Scarborough (I.P., Y.-R.J., S.R., H.Y., V.L.).
Sergey RyzhovMaine Medical Center Research Institute, Scarborough (I.P., Y.-R.J., S.R., H.Y., V.L.).
Haifeng YinMaine Medical Center Research Institute, Scarborough (I.P., Y.-R.J., S.R., H.Y., V.L.).
Beatriz PelachoProgram of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
David Gomez-Cabrero *Translational Bioinformatics Unit (TransBio), NavarraBiomed, Pamplona, Spain (X.M.d.M., M.L., N.P., D.G.-C.).
Volkhard Lindner *Maine Medical Center Research Institute, Scarborough (I.P., Y.-R.J., S.R., H.Y., V.L.).
David Lara-AstiasoAdvanced Genomics Laboratory (J.P.R., A.V.-Z., L.C.-L., P.S.M.-U., E.L.-V., D.L.-A.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Felipe Prósper *Program of Regenerative Medicine (A.R.-V., S.C.H., P.G.-O., E.I., G.A., G.M., B.P., F.P.), Program of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Navarre Institute of Health Research · ESMaine Medical Center · USNavarrabiomed · ESClinica Universidad de Navarra · ESCeMM Research Center for Molecular Medicine · ATJanssen (Belgium) · BEKU Leuven · BEUniversidad de Navarra · ES

Funding

The role of night shift work in metabolic disorders during and after pregnancyP20GM121301 · NIGMS · MAINEHEALTH · PI Lucy Liaw · 2017 to 2026
$25.1M
Progenitor Cell Analysis CoreP30GM106391 · NIGMS · MAINEHEALTH · PI WOJCHOWSKI, DON MICHAEL · 2013 to 2017
$5.7M
Neuregulin signaling in myeloid cellsR01HL136560 · NHLBI · MAINEHEALTH · PI Sergey Ryzhov · 2017 to 2026
$3.3M
Effect of CTHRC1 on endothelial cell survival after acute ischemiaR01HL146504 · NHLBI · MAINEHEALTH · PI LINDNER, VOLKHARD, RYZHOV, SERGEY · 2020 to 2023
$2.1M
NHLBI NIH HHS R01 HL136560NHLBI NIH HHS R01 HL146504NIGMS NIH HHS P20 GM121301NIGMS NIH HHS P30 GM106391
6 · The paper itself

Abstract

backgroundCardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heterogeneity in response to cardiac damage is lacking. The purpose of this study was to define CF heterogeneity during ventricular remodeling and the underlying mechanisms that regulate CF function.

methodsCollagen1α1-GFP (green fluorescent protein)-positive CFs were characterized after myocardial infarction (MI) by single-cell and bulk RNA sequencing, assay for transposase-accessible chromatin sequencing, and functional assays. Swine and patient samples were studied using bulk RNA sequencing.

resultsWe identified and characterized a unique CF subpopulation that emerges after MI in mice. These activated fibroblasts exhibit a clear profibrotic signature, express high levels of Cthrc1 (collagen triple helix repeat containing 1), and localize into the scar. Noncanonical transforming growth factor-β signaling and different transcription factors including SOX9 are important regulators mediating their response to cardiac injury. Absence of CTHRC1 results in pronounced lethality attributable to ventricular rupture. A population of CFs with a similar transcriptome was identified in a swine model of MI and in heart tissue from patients with MI and dilated cardiomyopathy.

conclusionsWe report CF heterogeneity and their dynamics during the course of MI and redefine the CFs that respond to cardiac injury and participate in myocardial remodeling. Our study identifies

Indexed as

RNA-SeqSingle-Cell AnalysisAnimalsCardiomyopathy, DilatedDisease Models, AnimalExtracellular Matrix ProteinsFibroblastsHumansMiceMyocardial InfarctionMyocardiumCTHRC1 protein, humanCthrc1 protein, mouseExtracellular Matrix Proteinsfibroblastsmyocardial infarctionsequence analysis, RNA

Identifiers

PMID32972203
PMCPMC7730974
OpenAlexW3088192190

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.