장지현 (Nationwide Children's Hospital) | 한빛사논문 > 한빛사

한빛사논문

조회317

Nationwide Children's Hospital

CV File 208 kb

Nat. Commun., May 16 2024, 15 (1) 4166 | https://doi.org/10.1038/s41467-024-48362-6 Endocardial HDAC3 is required for myocardial trabeculation

Jihyun Jang ^1,2, Mette Bentsen ³, Ye Jun Kim ⁴, Erick Kim ⁴, Vidu Garg^1,2, Chen-Leng Cai ⁵, Mario Looso³ & Deqiang Li ^1,2

¹Center for Cardiovascular Research, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43215, USA.

²Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA.

³Bioinformatics Core Unit (BCU), Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

⁵Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46201, USA.

Corresponding author

Correspondence to Deqiang Li.

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-20)
연구진국외 연구진
분야 생명과학 > 발생생물학

댓글 작성 로그인

CV 열람하기

연락처 보기