Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation

Abstract

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 signature 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.

Data availability

RNA Sequencing data have been deposited in GEO under accession code GSE136848We downloaded Tabula Muris data from https://github.com/czbiohub/tabula-muris and Betsholtz Lab data from NCBI Gene Expression Omnibus (GSE99235, GSE98816)

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

Article and author information

Author details

  1. Ankit Jambusaria

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zhigang Hong

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lianghui Zhang

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Shubhi Srivastava

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Arundhati Jana

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter T Toth

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yang Dai

    Department of Bioengineering, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Asrar B Malik

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    For correspondence
    abmalik@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8205-7128
  9. Jalees Rehman

    Department of Pharmacology, University of Illinois at Chicago, Chicago, United States
    For correspondence
    jalees@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2787-9292

Funding

National Institutes of Health (R01HL126516)

  • Jalees Rehman

National Institutes of Health (P01-HL60678)

  • Asrar B Malik
  • Jalees Rehman

National Institutes of Health (T32-HL007829)

  • Asrar B Malik

National Institutes of Health (R01-HL90152)

  • Asrar B Malik
  • Jalees Rehman

American Heart Association (18CDA34110068)

  • Lianghui Zhang

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

Ethics

Animal experimentation: All animal experiments were conducted in accordance with NIH guidelines for the Care and Use of Laboratory Animals and were performed in accordance with protocols approved by the Institutional Animal Care and Use Committees (IACUC) of the University of Illinois (protocol approval numbers 19-014, 13-175 and 16-064) .

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: August 27, 2019
  2. Accepted: January 15, 2020
  3. Accepted Manuscript published: January 16, 2020 (version 1)
  4. Version of Record published: February 5, 2020 (version 2)

Copyright

© 2020, Jambusaria 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. Ankit Jambusaria
  2. Zhigang Hong
  3. Lianghui Zhang
  4. Shubhi Srivastava
  5. Arundhati Jana
  6. Peter T Toth
  7. Yang Dai
  8. Asrar B Malik
  9. Jalees Rehman
(2020)
Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
eLife 9:e51413.
https://doi.org/10.7554/eLife.51413

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