ArticleeLife2022
A single cell transcriptional roadmap of human pacemaker cell differentiation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
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- Signaling mechanisms and dynamics governing the myocardial-epicardial fate switch during human cardiogenesis.Science advances · 2026Article
- Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis.Biology open · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Diffuse pacemaker mechanism with distinctive organization drives pulsation in the octocoralProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrative approaches in cardiac tissue engineering: Bridging cellular complexity to create accurate physiological models.iScience · 2025Review
- Article
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
- Bioengineering Approaches to In Vitro Modeling of Genetic and Acquired Cardiac Diseases.Current cardiology reports · 2025Review
- Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment.Stem cell reports · 2025Article
- Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.Nature communications · 2024Article
- Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.Cell stem cell · 2024Article
- The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development.Nature communications · 2024Article
- A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells.Signal transduction and targeted therapy · 2024Article
- Early heart development: examining the dynamics of function-form emergence.Biochemical Society transactions · 2024Review
- Differentiation of Sinoatrial-like Cardiomyocytes as a Biological Pacemaker Model.International journal of molecular sciences · 2024Review
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Each heartbeat is triggered by the sinoatrial node (SAN), the primary pacemaker of the heart. Studies in animal models have revealed that pacemaker cells share a common progenitor with the (pro)epicardium, and that the pacemaker cardiomyocytes further diversify into 'transitional', 'tail', and 'head' subtypes. However, the underlying molecular mechanisms, especially of human pacemaker cell development, are poorly understood. Here, we performed single cell RNA sequencing (scRNA-seq) and trajectory inference on human induced pluripotent stem cells (hiPSCs) differentiating to SAN-like cardiomyocytes (SANCMs) to construct a roadmap of transcriptional changes and lineage decisions. In differentiated SANCM, we identified distinct clusters that closely resemble different subpopulations of the in vivo SAN. Moreover, the presence of a side population of proepicardial cells suggested their shared ontogeny with SANCM, as also reported in vivo. Our results demonstrate that the divergence of SANCM and proepicardial lineages is determined by WNT signaling. Furthermore, we uncovered roles for TGFβ and WNT signaling in the branching of transitional and head SANCM subtypes, respectively. These findings provide new insights into the molecular processes involved in human pacemaker cell differentiation, opening new avenues for complex disease modeling in vitro and inform approaches for cell therapy-based regeneration of the SAN.
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