Evidence map›Paper›PMID 34230480›Full record

ArticleNature communications2021

Coordination of endothelial cell positioning and fate specification by the epicardium.

Pearl Quijada, Michael A Trembley, Adwiteeya Misra, Jacquelyn A Myers, Cameron D Baker, Marta Pérez-Hernández, Jason R Myers, Ronald A Dirkx, Ethan David Cohen, Mario Delmar and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

36 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Skin capillary endothelial cells form a network of spatiotemporally conserved CaProceedings of the National Academy of Sciences of the United States of America · 2026
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  13. Engineering a serum response factor superactivator of smooth muscle gene expression with a condensate-forming domain.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. LncRNAs in theInternational journal of molecular sciences · 2024
    Article
  18. Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024
    Review
  19. Review
  20. Review
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

12 authors at 4 institutions in 1 country.

Pearl QuijadaDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID 0000-0003-2477-2374
Michael A TrembleyDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Adwiteeya MisraDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Jacquelyn A MyersGenomics Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID 0000-0002-5005-028X
Cameron D BakerGenomics Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID 0000-0002-3792-4317
Marta Pérez-HernándezLeon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA.ORCID 0000-0001-6119-103X
Jason R MyersGenomics Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Ronald A DirkxDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Ethan David CohenDepartment of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Mario DelmarLeon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA.
John M AshtonGenomics Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID 0000-0001-9875-5994
Eric M SmallDepartment of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. eric_small@urmc.rochester.edu.ORCID 0000-0001-8593-0343
University of Rochester · USNew York University · USBroad Center · USRochester Institute of Technology · US

Funding

The University of Rochester's Clinical and Translational Science InstituteUL1TR002001 · NCATS · UNIVERSITY OF ROCHESTER · PI WILSON, KAREN M., ZAND, MARTIN S · 2016 to 2024
$34.6M
RESEARCH METHODS IN PEDIATRICS HEART DISEASET32HL007572 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Sarah D DE FERRANTI, Jane W. Newburger · 1985 to 2026
$13.0M
MULTIDISCIPLINARY TRAINING IN PULMONARY RESEARCHT32HL066988 · NHLBI · UNIVERSITY OF ROCHESTER · PI GEORAS, STEVE N, O'REILLY, MICHAEL A · 2001 to 2021
$8.1M
Training in Cellular, Biochemical and Molecular SciencesT32GM068411 · NIGMS · UNIVERSITY OF ROCHESTER · PI MAQUAT, LYNNE E · 2005 to 2019
$3.9M
Role of PKP2 in epicardial structure and functionR01HL136179 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DELMAR, MARIO, MORLEY, GREGORY E · 2017 to 2020
$3.1M
Roles of Endothelial and Smooth Muscle KATP Channels in Myocardial Ischemic InjuryR01HL146514 · NHLBI · LSU HEALTH SCIENCES CENTER · PI COETZEE, WILLIAM A, LEFER, DAVID JOSEPH · 2020 to 2023
$3.0M
Role of desmosomes in cardiac electrical functionR01HL134328 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DELMAR, MARIO, MORLEY, GREGORY E · 2016 to 2019
$2.6M
Dysregulation of common metabolic and transcriptional pathways in heart and lung fibrosisR01HL133761 · NHLBI · UNIVERSITY OF ROCHESTER · PI SMALL, ERIC M, WOELLER, COLLYNN FREMONT · 2016 to 2019
$2.1M
Regulation of epicardial cell differentiation during development and diseaseR01HL120919 · NHLBI · UNIVERSITY OF ROCHESTER · PI SMALL, ERIC M · 2014 to 2018
$1.9M
Coordination of inflammatory signaling and cardiac fibrosis by small proline rich proteinsR01HL144867 · NHLBI · UNIVERSITY OF ROCHESTER · PI SMALL, ERIC M · 2019 to 2022
$1.7M
The sodium channel ecosystem in the adult ventricular myocyteR01HL145911 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DELMAR, MARIO · 2019 to 2021
$1.5M
Defining the Unique Role of Fibroblasts in Neonatal Cardiac RegenerationF30HL150883 · NHLBI · UNIVERSITY OF ROCHESTER · PI MISRA, ADWITEEYA · 2020 to 2022
$145k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR002001NHLBI NIH HHS F30 HL150883NHLBI NIH HHS F32 HL134206NHLBI NIH HHS R01 HL120919NHLBI NIH HHS R01 HL133761NHLBI NIH HHS R01 HL134328NHLBI NIH HHS R01 HL136179NHLBI NIH HHS R01 HL144867NHLBI NIH HHS R01 HL145911NHLBI NIH HHS R01 HL146514NHLBI NIH HHS T32 HL007572NHLBI NIH HHS T32 HL066988NIGMS NIH HHS T32 GM068411
6 · The paper itself

Abstract

The organization of an integrated coronary vasculature requires the specification of immature endothelial cells (ECs) into arterial and venous fates based on their localization within the heart. It remains unclear how spatial information controls EC identity and behavior. Here we use single-cell RNA sequencing at key developmental timepoints to interrogate cellular contributions to coronary vessel patterning and maturation. We perform transcriptional profiling to define a heterogenous population of epicardium-derived cells (EPDCs) that express unique chemokine signatures. We identify a population of Slit2+ EPDCs that emerge following epithelial-to-mesenchymal transition (EMT), which we term vascular guidepost cells. We show that the expression of guidepost-derived chemokines such as Slit2 are induced in epicardial cells undergoing EMT, while mesothelium-derived chemokines are silenced. We demonstrate that epicardium-specific deletion of myocardin-related transcription factors in mouse embryos disrupts the expression of key guidance cues and alters EPDC-EC signaling, leading to the persistence of an immature angiogenic EC identity and inappropriate accumulation of ECs on the epicardial surface. Our study suggests that EC pathfinding and fate specification is controlled by a common mechanism and guided by paracrine signaling from EPDCs linking epicardial EMT to EC localization and fate specification in the developing heart.

Indexed as

AnimalsChemokinesCoronary VesselsEmbryo, MammalianEndothelial CellsEpithelial-Mesenchymal TransitionGene ExpressionHeartIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMyocardinNerve Tissue ProteinsNuclear ProteinsPericardiumSerum Response FactorChemokinesIntercellular Signaling Peptides and ProteinsMyocardinNerve Tissue ProteinsNuclear ProteinsSerum Response FactorSlit Homolog 2 ProteinSrf protein, mouseTrans-ActivatorsTranscription Factors

Identifiers

PMID34230480
PMCPMC8260743
OpenAlexW3181267383

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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.