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


Besides cardiomyocytes (CM), the heart contains numerous interstitial 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 (MI) surgery. Clustering of >30,000 single cells identified >30 populations representing nine cell lineages, including 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 uncovered novel myofibroblast subtypes expressing either pro-fibrotic or anti-fibrotic signatures. Our data highlight non-linear dynamics in myeloid and fibroblast lineages after cardiac injury, and provide an entry point for deeper analysis of cardiac homeostasis, inflammation, fibrosis, repair and regeneration.

Type Journal
ISBN 2050-084X (Electronic) 2050-084X (Linking)
Authors Farbehi, N.; Patrick, R.; Dorison, A.; Xaymardan, M.; Janbandhu, V.; Wystub-Lis, K.; Ho, J. W.; Nordon, R. E.; Harvey, R. P.
Responsible Garvan Author Nona Farbehi
Publisher Name eLife
Published Date 2019-03-26
Published Volume 8
Published Pages pii: 43882
Status Always Electronic
DOI 10.7554/eLife.43882
URL link to publisher's version