Transcriptional Regulation of the Postnatal Cardiac Conduction System Heterogeneity

Transcriptional Regulation of the Postnatal Cardiac Conduction System Heterogeneity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Transcriptional Regulation of the Postnatal Cardiac Conduction System Heterogeneity Kyoung-Han Kim, Yena Oh, Rimshah Abid, Saif Dababneh, Marwan Bakr, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2925397/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Aug, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract The cardiac conduction system (CCS) is a network of specialized cardiomyocytes coordinating electrical impulse 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 as well as regulators remain not fully understood. Here, we demonstrated the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncovered region-specific markers and zonation patterns of gene expression across the CCS, which were histologically validated. Network inference showed heterogeneous gene regulatory networks across the CCS. Notably, CCS region-specific gene regulation was recapitulated in a dish using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding was supported by ATAC-seq of different CCS regions, Tbx3-ChIP-seq, and the identification of Irx motifs. Overall, this study demonstrates comprehensive molecular profiles within the postnatal CCS and provides evidence of the regulatory mechanisms contributing to its heterogeneity. Biological sciences/Molecular biology/Transcriptomics Biological sciences/Genetics/Gene expression Biological sciences/Genetics/Gene regulation Biological sciences/Physiology/Cardiovascular biology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files sTable1Markersccs.xlsx Supplementary Table 1 sTable2SpatialTranscriptomicsCCSmarkers.xlsx Supplementary Table 2 sTable3EmbryonicvsPostnatal.xlsx Supplementary Table 3 sTable4SCENICMeanAUC.xlsx Supplementary Table 4 sTable5tdTomatoCresequence.xlsx Supplementary Table 5 sTable6qPCRprimers.xlsx Supplementary Table 6 NCOMMS2320776Ars.pdf Reporting Summary Cite Share Download PDF Status: Published Journal Publication published 02 Aug, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2925397","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":276697834,"identity":"d2b99e4e-4c21-4fff-8713-fe3797353a9d","order_by":0,"name":"Kyoung-Han 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