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

eLife

Gunnar W Klau¹  Jonas F Weber¹  Tobias Lautwein²  Karl Köhrer²  Zhaoping Ding³  Jürgen Schrader³  Julia Hesse³  Christoph Owenier³  Christina Alter³  Ria Zalfen³  Norbert Gerdes⁴  Alexander Lang⁴  Jens W Fischer⁵  Maria Grandoch⁵  Christoph Dieterich⁶ 

[1] Algorithmic Bioinformatics, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;Biologisch-Medizinisches-Forschungszentrum (BMFZ), Genomics & Transcriptomics Laboratory, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;Department of Molecular Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;Institute of Pharmacology and Clinical Pharmacology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany;Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology and Department of Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany;

关键词: myocardial infarction;    epicardium;    cardiac fibroblasts;    ScRNAseq;    transcriptomics;    Mouse;   

DOI  :  10.7554/eLife.65921

来源: eLife Sciences Publications, Ltd

【 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)-1α 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.

【 授权许可】

CC BY