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Publication : Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.

First Author  Oh Y Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  6550
PubMed ID  39095365 Mgi Jnum  J:357277
Mgi Id  MGI:7708482 Doi  10.1038/s41467-024-50849-1
Citation  Oh Y, et al. (2024) Transcriptional regulation of the postnatal cardiac conduction system heterogeneity. Nat Commun 15(1):6550
abstractText  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.
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