PT  - JOURNAL ARTICLE
AU  - Nadine Suffee
AU  - Thomas Moore-Morris
AU  - Nathalie Mougenot
AU  - Gilles Dilanian
AU  - Myriam Berthet
AU  - Bernd Jagla
AU  - Julie Proukhnitzky
AU  - Pascal Le Prince
AU  - David A Tregouet
AU  - Michel Pucéat
AU  - Stéphane N Hatem
TI  - Cell Specific Reactivation of Epicardium at the Origin of Fibro-Fatty Remodeling of the Atrial Myocardium
AID  - 10.1101/589705
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 589705
4099  - http://biorxiv.org/content/early/2019/03/28/589705.short
4100  - http://biorxiv.org/content/early/2019/03/28/589705.full
AB  - Epicardium, the mesothelium covering the heart, is composed of multipotent cells and is reactivated following myocardial injury in adults. Herein, we provide evidence for activation of atrial epicardium in aged patients with diseased atria and in murine models of atrial remodeling. Epicardial activation contributed to fibro-fatty infiltration of sub-epicardium that contained a number of cells co-expressing markers of epicardial progenitors and fibroblasts. Indeed, using genetic lineage tracing of adult epicardium, we demonstrate the epicardial origin of fibroblasts within fibro-fatty infiltrates. A subpopulation of adult epicardial-derived cells (aEPDCs) expressing PDGFRα, niched in the sub-epicardium, were isolated and differentiated into myofibroblast in the presence of angiotensin-II. Furthermore, single cell RNA-seq analysis identified several clusters of aEPDCs and revealed transition from adipogenic to fibrogenic cells. In conclusion, a subset of aEPDCs, pre-programmed towards a specific cell fate, contributes to fibro-fatty infiltration of sub-epicardium of diseased atria.