2026-05-22T01:43:03Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/253792025-12-18T12:55:46Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16969col_20.500.12105_19616

00925njm 22002777a 4500 dc Gomez-del Arco, Pablo author Isern, Joan author Jimenez-Carretero, Daniel author Lopez-Maderuelo, Dolores author Piñeiro-Sabarís, Rebeca author El Abdellaoui-Soussi, Fadoua author Torroja, Carlos author Vera-Pedrosa, María Linarejos author Grima-Terrén, Mercedes author Benguria, Alberto author Simón-Chica, Ana author Queiro-Palou, Antonio author Dopazo, Ana author Sanchez-Cabo, Fatima author Jalife, Jose author de la Pompa, Jose Luis author Filgueiras-Rama, David author Munoz-Canoves, Pura author Redondo, Juan Miguel author 2024-10-04 Extensive genetic studies have elucidated cardiomyocyte differentiation and associated gene networks using single-cell RNA-seq, yet the intricate transcriptional mechanisms governing cardiac conduction system (CCS) development and working cardiomyocyte differentiation remain largely unexplored. Here we show that mice deleted for Dhx36 (encoding the Dhx36 helicase) in the embryonic or neonatal heart develop overt dilated cardiomyopathy, surface ECG alterations related to cardiac impulse propagation, and (in the embryonic heart) a lack of a ventricular conduction system (VCS). Heart snRNA-seq and snATAC-seq reveal the role of Dhx36 in CCS development and in the differentiation of working cardiomyocytes. Dhx36 deficiency directly influences cardiomyocyte gene networks by disrupting the resolution of promoter G-quadruplexes in key cardiac genes, impacting cardiomyocyte differentiation and CCS morphogenesis, and ultimately leading to dilated cardiomyopathy and atrioventricular block. These findings further identify crucial genes and pathways that regulate the development and function of the VCS/Purkinje fiber (PF) network. Nat Commun. 2024 Oct 4;15(1):8602. 10.1038/s41467-024-52809-1 2041-1723 Nature Communications 39366945 https://hdl.handle.net/20.500.12105/25379 The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development