Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes

  1. Nora Yucel  Is a corresponding author
  2. Jessie Axsom
  3. Yifan Yang
  4. Li Li
  5. Joshua H Rhoades
  6. Zoltan Arany  Is a corresponding author
  1. University of Pennsylvania, United States

Abstract

Endothelial cells (ECs) are widely heterogenous depending on tissue and vascular localization. Jambusaria et al. recently demonstrated that ECs in various tissues surprisingly possess mRNA signatures of their underlying parenchyma. The mechanism underlying this observation remains unexplained, and could include mRNA contamination during cell isolation, in vivo mRNA paracrine transfer from parenchymal cells to ECs, or cell-autonomous expression of these mRNAs in ECs. Here, we use a combination of bulk RNASeq, single cell RNASeq datasets, in situ mRNA hybridization, and most importantly ATAC-Seq of FACS-isolated nuclei, to show that cardiac endothelial cells actively express cardiomyocyte myofibril (CMF) genes and have open chromatin at CMF gene promoters. These open chromatin sites are enriched for sites targeted by cardiac transcription factors, and close upon expansion of ECs in culture. Together, these data demonstrate unambiguously that the expression of CMF genes in ECs is cell-autonomous, and not simply a result of technical contamination or paracrine transfers of mRNAs, and indicate that local cues in the heart in vivo unexpectedly maintain fully open chromatin in ECs at genes previously thought limited to cardiomyocytes.

Data availability

Sequencing data have been deposited in GEO under accession number GSE144839.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Nora Yucel

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    For correspondence
    ndyucel@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1848-6462
  2. Jessie Axsom

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yifan Yang

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Li Li

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Joshua H Rhoades

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zoltan Arany

    Cardiovascular Institute, University of Pennsylvania, Philadelphia, United States
    For correspondence
    zarany@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1368-2453

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01HLDK114103)

  • Zoltan Arany

American Heart Association (AHA/Allen Initative)

  • Zoltan Arany

National Institutes of Health (T32 DKO7314)

  • Nora Yucel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#805255) of the University of Pennsylvania.

Reviewing Editor

  1. Victoria L Bautch, University of North Carolina, Chapel Hill, United States

Publication history

  1. Received: February 4, 2020
  2. Accepted: December 13, 2020
  3. Accepted Manuscript published: December 14, 2020 (version 1)
  4. Version of Record published: December 23, 2020 (version 2)

Copyright

© 2020, Yucel et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nora Yucel
  2. Jessie Axsom
  3. Yifan Yang
  4. Li Li
  5. Joshua H Rhoades
  6. Zoltan Arany
(2020)
Cardiac endothelial cells maintain open chromatin and expression of cardiomyocyte myofibrillar genes
eLife 9:e55730.
https://doi.org/10.7554/eLife.55730

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