2026-05-21T23:07:04Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Caixa
funder
Unión Europea. Comisión Europea. H2020
funder
Fundación La Marató TV3
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Agencia Estatal de Investigación (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Consejo Superior de Investigaciones Científicas (España)
funder
Autonomous University of Madrid (España)
funder
Sociedad Española de Cardiología
2024-10-30T12:53:52Z
2024-10-30T12:53:52Z
2024-10-04
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
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.
eng
The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development
research article
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