ArticleCirculation research2019
Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed.
- CMAC: A deep learning framework for absolute cardiomyocyte transcriptional age estimation.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.Biology open · 2026Article
- Decoding Cardiac Development and Maturation at Single-Cell and Spatial Transcriptomic Resolution.Circulation research · 2026Review
- AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents.The Journal of clinical investigation · 2026Article
- Mass spectrometric proteome profiling using a deep spectral library reveals homogenization of right and left atrial proteomes in persistent atrial fibrillation patients.Cardiovascular research · 2026Article
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Spatial transcriptomic profiling of developing mouse hearts reveals a spatially patterned signaling environment.Communications biology · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Neural signaling contributes to heart formation and growth in the invertebrate chordate, Ciona robusta.PLoS biology · 2026Article
- Cardiac conduction system malformations in heterotaxy result from dysregulated Pitx2 expression.JCI insight · 2026Article
- Article
- The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects.Genome research · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Spatiotemporal gene expression and cellular dynamics of the developing human heart.Nature genetics · 2025Article
- Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy.American journal of human genetics · 2025Article
- Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic Dysfunction.JACC. Basic to translational science · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- A spatiotemporal cell atlas of cardiopulmonary progenitor cell allocation during development.Cell reports · 2025Article
- Meis transcription factors regulate cardiac conduction system development and adult function.Cardiovascular research · 2025Article
- The Neglected Internodal Tract-A Cardiac Conduction System Structure Homologous to the Development and Regulation of the Sinoatrial Node.Reviews in cardiovascular medicine · 2025Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
rationaleThe cardiac conduction system (CCS) consists of distinct components including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers. Despite an essential role for the CCS in heart development and function, the CCS has remained challenging to interrogate because of inherent obstacles including small cell numbers, large cell-type heterogeneity, complex anatomy, and difficulty in isolation. Single-cell RNA-sequencing allows for genome-wide analysis of gene expression at single-cell resolution.
objectiveAssess the transcriptional landscape of the entire CCS at single-cell resolution by single-cell RNA-sequencing within the developing mouse heart. METHODS AND
resultsWild-type, embryonic day 16.5 mouse hearts (n=6 per zone) were harvested and 3 zones of microdissection were isolated, including: Zone I-sinoatrial node region; Zone II-atrioventricular node/His region; and Zone III-bundle branch/Purkinje fiber region. Tissue was digested into single-cell suspensions, cells isolated, mRNA reverse transcribed, and barcoded before high-throughput sequencing and bioinformatics analyses. Single-cell RNA-sequencing was performed on over 22 000 cells, and all major cell types of the murine heart were successfully captured including bona fide clusters of cells consistent with each major component of the CCS. Unsupervised weighted gene coexpression network analysis led to the discovery of a host of novel CCS genes, a subset of which were validated using fluorescent in situ hybridization as well as whole-mount immunolabeling with volume imaging (iDISCO+) in 3 dimensions on intact mouse hearts. Further, subcluster analysis unveiled isolation of distinct CCS cell subtypes, including the clinically relevant but poorly characterized transitional cells that bridge the CCS and surrounding myocardium.
conclusionsOur study represents the first comprehensive assessment of the transcriptional profiles from the entire CCS at single-cell resolution and provides a characterization in the context of development and disease.
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