Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury
Nona Farbehi,
Ralph Patrick,
Aude Dorison,
Munira Xaymardan,
Vaibhao Janbandhu,
Katharina Wystub-Lis,
Joshua WK Ho,
Robert E Nordon,
Richard P Harvey
Affiliations
Nona Farbehi
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; Garvan Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia; Graduate School of Biomedical Engineering, UNSW Sydney, Kensington, Australia
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; St. Vincent's Clinical School, UNSW Sydney, Kensington, Australia
Aude Dorison
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia
Munira Xaymardan
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; School of Dentistry, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, Australia
Vaibhao Janbandhu
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; St. Vincent's Clinical School, UNSW Sydney, Kensington, Australia
Katharina Wystub-Lis
Victor Chang Cardiac Research Institute, Darlinghurst, Australia
Joshua WK Ho
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent's Clinical School, UNSW Sydney, Kensington, Australia
Robert E Nordon
Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; Graduate School of Biomedical Engineering, UNSW Sydney, Kensington, Australia
Victor Chang Cardiac Research Institute, Darlinghurst, Australia; Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia; School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, Australia
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.
