Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted murine heart

被引：53

作者：

Hesse, Julia ^{[1
,2
]}

Owenier, Christoph ^{[1
,2
]}

Lautwein, Tobias ^{[3
]}

Zalfen, Ria ^{[1
,2
]}

Weber, Jonas F. ^{[4
]}

Ding, Zhaoping ^{[1
,2
]}

Alter, Christina ^{[1
,2
]}

Lang, Alexander ^{[2
,5
]}

Grandoch, Maria ^{[2
,6
]}

Gerdes, Norbert ^{[2
,5
]}

Fischer, Jens W. ^{[2
,6
]}

Klau, Gunnar W. ^{[4
]}

Dieterich, Christoph ^{[7
,8
]}

Koehrer, Karl ^{[3
]}

Schrader, Juergen ^{[1
,2
]}

机构：

[1] Heinrich Heine Univ Dusseldorf, Med Fac, Dept Mol Cardiol, Dusseldorf, Germany

[2] Heinrich Heine Univ Dusseldorf, Univ Hosp Dusseldorf, Dusseldorf, Germany

[3] Heinrich Heine Univ Dusseldorf, Genom & Transcript Lab, Biolog Med Forsch Zentrum BMFZ, Dusseldorf, Germany

[4] Heinrich Heine Univ Dusseldorf, Algorithm Bioinformat, Dusseldorf, Germany

[5] Heinrich Heine Univ Dusseldorf, Div Cardiol Pulmonol & Vasc Med, Med Fac, Dusseldorf, Germany

[6] Heinrich Heine Univ Dusseldorf, Med Fac, Inst Pharmacol & Clin Pharmacol, Dusseldorf, Germany

[7] Univ Hosp Heidelberg, Klaus Tschira Inst Integrat Computat Cardiol, Sect Bioinformat & Syst Cardiol, Heidelberg, Germany

[8] Univ Hosp Heidelberg, Dept Internal Med 3, Heidelberg, Germany

来源：

ELIFE | 2021年 / 10卷

关键词：

FACTOR-I; CARDIAC FIBROBLASTS; MYOCARDIAL INJURY; CARDIOMYOCYTES; EXPRESSION; CONTRIBUTE; DIVERSITY; PLATFORM; GENES; WT1;

D O I：

10.7554/eLife.65921

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In the adult heart, the epicardium becomes activated after injury, contributing to cardiac healing by secretion of paracrine factors. Here, we analyzed by single-cell RNA sequencing combined with RNA in situ hybridization and lineage tracing of Wilms tumor protein 1-positive (WT1(+)) cells, the cellular composition, location, and hierarchy of epicardial stromal cells (EpiSC) in comparison to activated myocardial fibroblasts/stromal cells in infarcted mouse hearts. We identified 11 transcriptionally distinct EpiSC populations, which can be classified into three groups, each containing a cluster of proliferating cells. Two groups expressed cardiac specification markers and sarcomeric proteins suggestive of cardiomyogenic potential. Transcripts of hypoxia-inducible factor (HIF)-1 alpha and HIF-responsive genes were enriched in EpiSC consistent with an epicardial hypoxic niche. Expression of paracrine factors was not limited to WT1(+) cells but was a general feature of activated cardiac stromal cells. Our findings provide the cellular framework by which myocardial ischemia may trigger in EpiSC the formation of cardioprotective/regenerative responses.

引用

页数：21

共 49 条

[1]

Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/nmeth.4463, 10.1038/NMETH.4463]

[2] A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart [J].