First Author | Hesse J | Year | 2021 |
Journal | Elife | Volume | 10 |
PubMed ID | 34152268 | Mgi Jnum | J:350636 |
Mgi Id | MGI:6728157 | Doi | 10.7554/eLife.65921 |
Citation | Hesse J, et al. (2021) Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted murine heart. Elife 10 |
abstractText | 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)-1alpha 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. |