학술논문
Endocardial HDAC3 is required for myocardial trabeculation.
Document Type
Academic Journal
Author
Jang J; Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43215, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, 43215, USA.; Bentsen M; Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.; Kim YJ; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; Kim E; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; Garg V; Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43215, USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, 43215, USA.; Cai CL; Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46201, USA.; Looso M; Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.; Li D; Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, 43215, USA. deqiang.li@nationwidechildrens.org.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, 43215, USA. deqiang.li@nationwidechildrens.org.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
Failure of proper ventricular trabeculation is often associated with congenital heart disease. Support from endocardial cells, including the secretion of extracellular matrix and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of extracellular matrix and growth factors is initiated and regulated by endocardial cells. We find that genetic knockout of histone deacetylase 3 in the endocardium in mice results in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identifies significant downregulation of extracellular matrix components in histone deacetylase 3 knockout endocardial cells. Secretome from cultured histone deacetylase 3 knockout mouse cardiac endothelial cells lacks transforming growth factor ß3 and shows significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which is remarkably rescued by transforming growth factor ß3 supplementation. Mechanistically, we identify that histone deacetylase 3 knockout induces transforming growth factor ß3 expression through repressing microRNA-129-5p. Our findings provide insights into the pathogenesis of congenital heart disease and conceptual strategies to promote myocardial regeneration.
(© 2024. The Author(s).)
(© 2024. The Author(s).)