Transcriptional regulation of the postnatal cardiac conduction system heterogeneity

Yena Oh, Rimshah Abid, Saif Dababneh, Marwan Bakr, Termeh Aslani, David P. Cook, Barbara C. Vanderhyden, Jin G. Park, Nikhil V. Munshi, Chi-Chung Hui and Kyoung-Han Kim ()
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Yena Oh: University of Ottawa Heart Institute
Rimshah Abid: University of Ottawa Heart Institute
Saif Dababneh: University of Ottawa Heart Institute
Marwan Bakr: University of Ottawa Heart Institute
Termeh Aslani: University of Ottawa Heart Institute
David P. Cook: University of Ottawa
Barbara C. Vanderhyden: University of Ottawa
Jin G. Park: Arizona State University
Nikhil V. Munshi: UT Southwestern Medical Center
Chi-Chung Hui: The Hospital for Sick Children
Kyoung-Han Kim: University of Ottawa Heart Institute

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-50849-1

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