期刊
ELIFE
卷 8, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.43882
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资金
- University of New South Wales
- National Health and Medical Research Council [1105271, 573707, 1118576, 1074386]
- Stem Cells Australia [SR110001002]
- Fondation Leducq [15CVD03, 13CVD01]
- St. Vincent's Clinic Foundation [100711]
- National Heart Foundation of Australia [100848]
- New South Wales Cardiovascular Research Network
- National Health and Medical Research Council of Australia [1105271, 1118576] Funding Source: NHMRC
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.
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