1. Cell Biology
  2. Chromosomes and Gene Expression

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
https://doi.org/10.7554/eLife.55730
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Cite this article
  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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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.

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

Share this article

https://doi.org/10.7554/eLife.55730

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Further reading

    1. Immunology and Inflammation

    Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation

    Ankit Jambusaria, Zhigang Hong ... Jalees Rehman
    Research Article Updated

    Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which can be visualized at http://www.rehmanlab.org/ribo. We found that endothelial cells express genes typically found in the surrounding tissues such as synaptic vesicle genes in the brain endothelium and cardiac contractile genes in the heart endothelium. Complementary analysis of endothelial single cell RNA-Seq data identified the molecular signatures shared across the endothelial translatome and single cell transcriptomes. The tissue-specific heterogeneity of the endothelium is maintained during systemic in vivo inflammatory injury as evidenced by the distinct responses to inflammatory stimulation. Our study defines endothelial heterogeneity and plasticity and provides a molecular framework to understand organ-specific vascular disease mechanisms and therapeutic targeting of individual vascular beds.