Epicardial cell lineages and the origin of the coronary endothelium

Rita Carmona, Silvia Barrena, Antonio Jesús López Gambero, Anabel Rojas, Ramón Muñoz‐Chápuli
The FASEB Journal. 2020-02-18; 34(4): 5223-5239
DOI: 10.1096/fj.201902249RR

PubMed

Lire sur PubMed

Carmona R(1)(2)(3), Barrena S(1)(2)(3), López Gambero AJ(1)(2)(3), Rojas A(4)(5), Muñoz-Chápuli R(1)(2)(3).

Author information:
(1)Department of Animal Biology, Faculty of Science, University of Málaga,
Málaga, Spain.
(2)Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga,
Spain.
(3)Institute of Biomedical Research of Málaga (IBIMA), Málaga, Spain.
(4)Andalusian Center of Molecular Biology and Regenerative Medicine (CABIMER),
Sevilla, Spain.
(5)Center for Biomedical Research in Diabetes and Associated Metabolic Disorders
(CIBERDEM), Sevilla, Spain.

The embryonic epicardium generates a population of epicardial-derived
mesenchymal cells (EPDC) whose contribution to the coronary endothelium is minor
or, according to some reports, negligible. We have compared four murine
cell-tracing models related to the EPDC in order to elucidate this contribution.
Cre recombinase was expressed under control of the promoters of the Wilms’ tumor
suppressor (Wt1), the cardiac troponin (cTnT), and the GATA5 genes, activating
expression of the R26REYFP reporter. We have also used the G2 enhancer of the
GATA4 gene as a driver due to its activation in the proepicardium. Recombination
was found in most of the epicardium/EPDC in all cases. The contribution of these
lineages to the cardiac endothelium was analyzed using confocal microscopy and
flow cytometry. G2-GATA4 lineage cells are the most frequent in the endothelium,
probably due to the recruitment of circulating endothelial progenitors. The
contribution of the WT1 cell lineage increases along gestation due to further
endothelial expression of WT1. GATA5 and cTnT lineages represent 4% of the
cardiac endothelial cells throughout the gestation, probably standing for the
actual EPDC contribution to the coronary endothelium. These results suggest
caution when using a sole cell-tracing model to study the fate of the EPDC.