RT Journal Article T1 CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells. A1 Junghof, Julia A1 Kogure, Yuta A1 Yu, Tian A1 Verdugo-Sivianes, Eva Maria A1 Narita, Megumi A1 Lucena-Cacace, Antonio A1 Yoshida, Yoshinori K1 Cell signalling K1 Transcriptomics K1 Stem-cell differentiation K1 Regenerative medicine AB The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) via epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a biomarker defining lineage specification in human active epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results highlight the importance of tracing CDH18 expression in hiPSC-derived epicardial cells, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine. PB Nature Publishing Group YR 2022 FD 2022-02-02 LK http://hdl.handle.net/10668/19558 UL http://hdl.handle.net/10668/19558 LA en NO Junghof J, Kogure Y, Yu T, Verdugo-Sivianes EM, Narita M, Lucena-Cacace A, et al. CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells. NPJ Regen Med. 2022 Feb 2;7(1):14. DS RISalud RD Apr 10, 2025