Key result
Novel transgenic mouse model enables isolation and immortalization of distinct epicardium-derived cardiac fibroblasts.
Why the study?
Embryonic epicardium is a major source of cardiac fibroblasts, but models to study distinct epicardium-derived fibroblast populations in vitro are lacking.
The study presents a novel immortalized in vitro mouse model to investigate the activation, identity, and functional properties of epicardium-derived cardiac fibroblasts.
New model enables in vitro study of epicardial fibroblast subsets; extends preclinical tools but leaves clinical translation open.
Embryonic epicardium is a major source of cardiac fibroblasts (CFs), which play essential roles in heart development and response to heart injury. In this study, we developed a novel mouse model to identify distinct populations of epicardium-derived CFs. Our Wt1 GFP/+ ;Wt1Cre;ROSA26-tdRFP model enables lineage tracing of WT1Cre-labeled (RFP + ) fibroblasts and the identification of cells actively expressing WT1 (GFP + ). Flow cytometry at early postnatal stages showed that RFP + cells form a heterogeneous stromal population, with 20.13% co-expressing GFP, indicating persistent WT1 expression in a subset. We successfully immortalized RFP + cardiac stromal cells, highly enriched in fibroblasts, by excluding other Wt1Cre-active cell types. Through culture condition optimization, we could selectively expand or differentiate specific fibroblast subpopulations, increasing the model’s utility. These immortalized cells, carrying an integrated WT1 reporter system, provide a robust in vitro platform to study fibroblast activation, differentiation, and plasticity under defined conditions. Summary blurb This study presents a novel in vitro mouse model for investigating the activation, identity, and functional properties of epicardium-derived cardiac fibroblasts.
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Müller‐Sánchez et al. (2025) studied Cardiac fibroblasts (in vitro model). Wt1GFP/+;Wt1Cre;ROSA26-tdRFP mouse model was evaluated on Identification and immortalization of distinct populations of epicardium-derived cardiac fibroblasts. A novel Wt1GFP/+;Wt1Cre;ROSA26-tdRFP mouse model successfully enabled the isolation and immortalization of distinct populations of epicardium-derived cardiac fibroblasts for in vitro study.
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