Format

Send to

Choose Destination
Elife. 2019 Mar 26;8. pii: e43882. doi: 10.7554/eLife.43882.

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

Farbehi N#1,2,3,4, Patrick R#1,2,5, Dorison A1,2, Xaymardan M1,2,6, Janbandhu V1,2,5, Wystub-Lis K1, Ho JW1,5, Nordon RE2,4, Harvey RP1,2,7.

Author information

1
Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
2
Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, Victoria, Australia.
3
Garvan Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, Australia.
4
Graduate School of Biomedical Engineering, UNSW Sydney, Kensington, Australia.
5
St. Vincent's Clinical School, UNSW Sydney, Kensington, Australia.
6
School of Dentistry, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, Australia.
7
School of Biotechnology and Biomolecular Science, UNSW Sydney, Kensington, Australia.
#
Contributed equally

Abstract

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.

KEYWORDS:

cell biology; computational biology; heart; mouse; myocardial infarction; scRNA-seq; systems biology

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center