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

被引：406

作者：

Farbehi, Nona ^{[1
,2
,3
,4
]}

Patrick, Ralph ^{[1
,2
,5
]}

Dorison, Aude ^{[1
,2
]}

Xaymardan, Munira ^{[1
,2
,6
]}

Janbandhu, Vaibhao ^{[1
,2
,5
]}

Wystub-Lis, Katharina ^{[1
]}

Ho, Joshua W. K. ^{[1
,5
]}

Nordon, Robert E. ^{[2
,4
]}

Harvey, Richard P. ^{[1
,2
,7
]}

机构：

[1] Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia

[2] Univ Melbourne, Stem Cells Australia, Melbourne Brain Ctr, Melbourne, Vic, Australia

[3] Garvan Inst Med Res, Garvan Weizmann Ctr Cellular Genom, Sydney, NSW, Australia

[4] UNSW Sydney, Grad Sch Biomed Engn, Kensington, NSW, Australia

[5] UNSW Sydney, St Vincents Clin Sch, Kensington, NSW, Australia

[6] Univ Sydney, Westmead Hosp, Fac Med & Hlth, Sch Dent, Westmead, NSW, Australia

[7] UNSW Sydney, Sch Biotechnol & Biomol Sci, Kensington, NSW, Australia

来源：

ELIFE | 2019年 / 8卷

基金：

英国医学研究理事会;

关键词：

DISEASE JACC MACROPHAGE; STEADY-STATE; HEART; MONOCYTES; FIBROBLASTS; FIBROSIS; INFLAMMATION; REGENERATION; MYOCARDIUM; TRANSITION;

D O I：

10.7554/eLife.43882

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：39

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