Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

  1. Nona Farbehi
  2. Ralph Patrick
  3. Aude Dorison
  4. Munira Xaymardan
  5. Vaibhao Janbandhu
  6. Katharina Wystub-Lis
  7. Joshua W K Ho
  8. Robert E Nordon  Is a corresponding author
  9. Richard P Harvey  Is a corresponding author
  1. Victor Chang Cardiac Research Institute, Australia
  2. University of New South Wales, Australia

Abstract

Besides cardiomyocytes (CM), the heart contains numerous stromal cell types which play key roles in heart repair, regeneration and disease, including fibroblast, vascular and immune cells. However, a comprehensive understanding of this interactive cell community is lacking. We performed single cell RNA-sequencing of the total non-CM fraction and enriched (Pdgfra-GFP+) fibroblast lineage cells from murine hearts at days 3 and 7 post-sham or myocardial infarction surgery. Clustering of >30,000 single cells allowed us to identify >30 populations representing 9 cell lineages, included a previously undescribed fibroblast lineage trajectory present in both sham and MI hearts leading to a uniquely activated cell state defined in part by a strong anti-WNT transcriptome signature. We also defined three novel myofibroblast subtypes expressing either pro-fibrotic or anti-fibrotic signatures, and 8 macrophage subsets. These comprehensive cardiac single cell transcriptome data provide an entry point for deeper analysis of cardiac homeostasis, inflammation, fibrosis, repair and regeneration.

Data availability

Sequencing data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress) under accession codes E-MTAB-7376 and E-MTAB-7365.

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

Article and author information

Author details

  1. Nona Farbehi

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  2. Ralph Patrick

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0956-1026
  3. Aude Dorison

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  4. Munira Xaymardan

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  5. Vaibhao Janbandhu

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  6. Katharina Wystub-Lis

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  7. Joshua W K Ho

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    No competing interests declared.
  8. Robert E Nordon

    Graduate School of Biomedical Engineering, University of New South Wales, Kensington, Australia
    For correspondence
    r.nordon@unsw.edu.au
    Competing interests
    No competing interests declared.
  9. Richard P Harvey

    Developmental and Stem Cell Biology, Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    For correspondence
    r.harvey@victorchang.edu.au
    Competing interests
    Richard P Harvey, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9950-9792

Funding

Stem Cells Australia (SR110001002)

  • Richard P Harvey

National Health and Medical Research Council (1118576)

  • Richard P Harvey

National Health and Medical Research Council (1074386)

  • Richard P Harvey

Fondation Leducq (15CVD03)

  • Richard P Harvey

National Heart Foundation of Australia (100848)

  • Joshua W K Ho

St. Vincent's Clinic Foundation and New South Wales Government Cardiovascular Research Network (100711)

  • Richard P Harvey

University of New South Wales

  • Nona Farbehi

Fondation Leducq (13CVD01)

  • Richard P Harvey

National Health and Medical Research Council (1105271)

  • Joshua W K Ho

National Health and Medical Research Council (573707)

  • Richard P Harvey

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

Reviewing Editor

  1. Edward Morrisey, University of Pennsylvania, United States

Ethics

Animal experimentation: This research was performed following the guidelines, and with the approval, of the Garvan Institute of Medical Research/St. Vincent's Animal Experimentation Ethics Committee (research approvals 13/01, 13/02, 16/03 and 16/10).

Version history

  1. Received: November 26, 2018
  2. Accepted: March 25, 2019
  3. Accepted Manuscript published: March 26, 2019 (version 1)
  4. Version of Record published: April 11, 2019 (version 2)

Copyright

© 2019, Farbehi 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. Nona Farbehi
  2. Ralph Patrick
  3. Aude Dorison
  4. Munira Xaymardan
  5. Vaibhao Janbandhu
  6. Katharina Wystub-Lis
  7. Joshua W K Ho
  8. Robert E Nordon
  9. Richard P Harvey
(2019)
Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury
eLife 8:e43882.
https://doi.org/10.7554/eLife.43882

Share this article

https://doi.org/10.7554/eLife.43882

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