ArticleNature biotechnology2013
Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18.
Article in Nature biotechnology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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Who cites it
171 citing papers in PubMed, 332 citations in OpenAlex.
- Prevention of atrial fibrillation after open-chest surgery with extracellular vesicle therapy.JCI insight · 2023Trial
- The TBX18/SIX1 Transcriptional Circuit Maintains Stemness and EMT States to Promote Radioresistance in ESCC.Cancers · 2026Article
- AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents.The Journal of clinical investigation · 2026Article
- Nr2f1a and Isl1 repress acquisition of epicardial identity in venous atrial cardiomyocytes.Development (Cambridge, England) · 2026Article
- Biomechanical Isolation is Required for Maintenance of the Cardiac Pacemaker Cell Fate.Research square · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Hedgehog and Bmp signaling pathways play opposing roles during establishment of the cardiac inflow tract in zebrafish.Development (Cambridge, England) · 2026Article
- Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells.NPJ systems biology and applications · 2026Article
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Understanding normal cardiac morphogenesis and its disruptions: a journey through pathways.Frontiers in genetics · 2026Review
- Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models.Nature communications · 2025Article
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Tissue elasticity modulates cardiac pacemaker cell automaticity.American journal of physiology. Heart and circulatory physiology · 2025Article
- Review
- Gene Therapy for Cardiovascular Disease: Clinical Perspectives.Yonsei medical journal · 2024Review
- Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.Nature biomedical engineering · 2024Article
- Differentiation of Sinoatrial-like Cardiomyocytes as a Biological Pacemaker Model.International journal of molecular sciences · 2024Review
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Article
- Heart rhythmFrontiers in cardiovascular medicine · 2024Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The heartbeat originates within the sinoatrial node (SAN), a small structure containing <10,000 genuine pacemaker cells. If the SAN fails, the ∼5 billion working cardiomyocytes downstream of it become quiescent, leading to circulatory collapse in the absence of electronic pacemaker therapy. Here we demonstrate conversion of rodent cardiomyocytes to SAN cells in vitro and in vivo by expression of Tbx18, a gene critical for early SAN specification. Within days of in vivo Tbx18 transduction, 9.2% of transduced, ventricular cardiomyocytes develop spontaneous electrical firing physiologically indistinguishable from that of SAN cells, along with morphological and epigenetic features characteristic of SAN cells. In vivo, focal Tbx18 gene transfer in the guinea-pig ventricle yields ectopic pacemaker activity, correcting a bradycardic disease phenotype. Myocytes transduced in vivo acquire the cardinal tapering morphology and physiological automaticity of native SAN pacemaker cells. The creation of induced SAN pacemaker (iSAN) cells opens new prospects for bioengineered pacemakers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.