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- Title
Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted murine heart.
- Authors
Hesse, Julia; Owenier, Christoph; Lautwein, Tobias; Zalfen, Ria; Weber, Jonas F.; Zhaoping Ding; Alter, Christina; Lang, Alexander; Grandoch, Maria; Gerdes, Norbert; Fischer, Jens W.; Klau, Gunnar W.; Dieterich, Christoph; Köhrer, Karl; Schrader, Jürgen
- Abstract
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.
- Subjects
MYOCARDIAL ischemia; STROMAL cells; TUMOR proteins; RNA sequencing; HYPOXIA-inducible factors; HEART cells; FIBROBLASTS; HEART
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.65921