Electroconductive patch promotes heart repair by directing epicardial cells toward endothelial fate

Whether epicardium-derived cells (EPDCs) can differentiate into endothelial cells after myocardial infarction (MI) remains unclear. Considering the heart's electrical dependence, we asked if restoring electrical conduction could direct this potential. Using cardiac patches with tunable electroconductivity and genetic fate-mapping approaches in mice, we found that patches matching native myocardial electroconductivity (10^-4-10^-3 S/cm) specifically promoted proliferation and endothelial differentiation of WT1⁺ EPDCs, rescuing cardiac function. Single-cell transcriptomic sequencing revealed that electroconductive patches drove WT1⁺ EPDCs into a distinct WT1⁺TRPC3⁺CD93⁺ transitional state. These cells differentiated into endothelial cells via TRPC3-Ca²⁺ signaling and integrated into functional vessels. Inhibiting TRPC3 blocked differentiation and reduced infarct vascularization. Thus, improving electrical conduction unlocks and directs the endothelial differentiation of WT1⁺ EPDCs, offering a strategy for post-MI repair.