RT Journal Article T1 Intramyocardial Sprouting Tip Cells Specify Coronary Arterialization. A1 Cano-Rincón, Elena A1 Schwarzkopf, Jennifer A1 Kanda, Masatoshi A1 Lindberg, Eric A1 Hollfinger, Irene A1 Pogontke Díaz, Cristina A1 Braeuning, Caroline A1 Fischer, Cornelius A1 Hübner, Norbert A1 Gerhardt, Holger K1 Arterias coronarias AB The elaborate patterning of coronary arteries critically supports the high metabolic activity of the beating heart. How coronary endothelial cells coordinate hierarchical vascular remodeling and achieve arteriovenous specification remains largely unknown. Understanding the molecular and cellular cues that pattern coronary arteries is crucial to develop innovative therapeutic strategies that restore functional perfusion within the ischemic heart.Results: We discover that coronary arteries originate from cells that have previously transitioned through a specific tip cell phenotype. We identify nonoverlapping intramyocardial and subepicardial tip cell populations with differential gene expression profiles and regulatory pathways. Esm1-lineage tracing confirmed that intramyocardial tip cells selectively contribute to coronary arteries and endocardial tunnels, but not veins. Notably, prearterial cells are detected from development stages to adulthood, increasingly in response to ischemic injury, and in human embryos, suggesting that tip cell-to-artery specification is a conserved mechanism.Conclusions: A tip cell-to-artery specification mechanism drives arterialization of the intramyocardial plexus and endocardial tunnels throughout life and is reactivated upon ischemic injury. Differential sprouting programs govern the formation and specification of the venous and arterial coronary plexus. PB American Heart Association YR 2024 FD 2024 LK https://hdl.handle.net/10630/34033 UL https://hdl.handle.net/10630/34033 LA eng NO This project was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, SFB1366—B06 and SFB1470—A04) and by the Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK; German Center for Cardiovascular Research). E. Cano was also supported by a Postdoctoral Fellowship from Ramon Areces Foundation. DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 19 ene 2026