Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury
- Victor Chang Cardiac Research Institute, Australia
- 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.
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Single-cell RNA-seq of Pdgfra+/Sca1+/Cd31- mouse cardiac cellsArrayExpress database, E-MTAB-7365.
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Single cell RNA-Seq of the murine non-myocyte cardiac cellulomeArrayExpress database, E-MTAB-6173.
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Multicellular Transcriptional Analysis of Mammalian Heart RegenerationGene Expression Omnibus, GSE95755.
Article and author information
Author details
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
- 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
- Received: November 26, 2018
- Accepted: March 25, 2019
- Accepted Manuscript published: March 26, 2019 (version 1)
- 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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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
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