Transcriptional regulation of the postnatal cardiac conduction system heterogeneity

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, an...

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Vydané v:	Nature communications Ročník 15; číslo 1; s. 6550 - 18
Hlavní autori:	Oh, Yena, Abid, Rimshah, Dababneh, Saif, Bakr, Marwan, Aslani, Termeh, Cook, David P., Vanderhyden, Barbara C., Park, Jin G., Munshi, Nikhil V., Hui, Chi-Chung, Kim, Kyoung-Han
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 02.08.2024 Nature Publishing Group Nature Portfolio
Predmet:	14/1 14/32 14/63 45/91 49/31 49/39 631/208/199 631/208/200 631/337/2019 631/443/592 64/60 82/80 Animals Animals, Newborn Atrioventricular Node - metabolism Bundle of His - metabolism Cardiac muscle Cardiomyocytes Electric pulses Fibers Gene expression Gene Expression Regulation Gene regulation Gene Regulatory Networks Heart Heart Conduction System - metabolism Heterogeneity Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humanities and Social Sciences Mice multidisciplinary Myocytes Myocytes, Cardiac - metabolism Neonates Purkinje fibers Purkinje Fibers - metabolism Purkinje Fibers - physiology Regulatory mechanisms (biology) Science Science (multidisciplinary) Single-Cell Analysis Sinoatrial Node - metabolism Spatial data T-Box Domain Proteins - genetics T-Box Domain Proteins - metabolism Transcription factors Transcription Factors - genetics Transcription Factors - metabolism Transcriptome Transcriptomics Ventricle Zonation
ISSN:	2041-1723, 2041-1723
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Shrnutí:	The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncover region-specific markers and zonation patterns of expression. Network inference shows heterogeneous gene regulatory networks across the CCS. Notably, region-specific gene regulation is recapitulated in vitro using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding is supported by ATAC-seq of different CCS regions, Tbx3 ChIP-seq, and Irx motifs. Overall, this study provides comprehensive molecular profiles of the postnatal CCS and elucidates gene regulatory mechanisms contributing to its heterogeneity. The cardiac conduction system consists of specialized cardiomyocytes that synchronize heart contractions. Here, Oh et al . provide comprehensive molecular profiles of the postnatal cardiac conduction system and elucidate gene regulatory mechanisms contributing to its heterogeneity.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-50849-1