ArticleEMBO molecular medicine2015
Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 2 of them syntheses that pooled it.
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Who cites it
222 citing papers in PubMed, 2 syntheses or guidelines pooled it, 370 citations in OpenAlex.
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure.Cardiovascular research · 2019Guideline
- The p.Arg52Leu variant in GNB2 causes a gain-of-function due to an increase of IBMC cardiovascular disorders · 2026Article
- In silico modelling of multi-electrode arrays for enhancing cardiac drug testing on hiPSC-CM heterogeneous tissues.The Journal of physiology · 2026Article
- Review
- Optogenetic tachypacing facilitates burst-induced arrhythmia in stem cell-derived human atrial engineered heart tissue.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Identification of a Novel Genetic Variant Responsible for Familial Atrial Fibrillation.The Canadian journal of cardiology · 2026Article
- Nr2f1a and Isl1 repress acquisition of epicardial identity in venous atrial cardiomyocytes.Development (Cambridge, England) · 2026Article
- Human iPSCs: atrial versus ventricular cardiomyocytes and their functional and pharmacological differences.Biochemical Society transactions · 2026Review
- Positive inotropic effects of serotonin in atrial EHT: further proof for an atrial phenotype?Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Versatile hiPSC Models and Bioengineering Platforms for Investigation of Atrial Fibrosis and Fibrillation.Cells · 2026Review
- Reduced TBX5 dosage undermines developmental control of atrial cardiomyocyte identity in a model of human atrial disease.Development (Cambridge, England) · 2026Article
- Isolation and Culture of Neonatal Mouse Atrial and Ventricular Myocytes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Coordination of cardiogenesis in vivo and in vitro.Nature reviews. Molecular cell biology · 2026Review
- Article
- Recent Advances of Pluripotent Stem Cell-Derived Cardiomyocytes for Regenerative Medicine.Metabolites · 2025Review
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Technologies and applications of current human cardiac organoids.Acta pharmaceutica Sinica. B · 2025Review
- Human iPSC-Based in Vitro Cardiovascular Tissue Models for Drug Screening Applications.Current cardiology reports · 2025Review
- Review
162 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Drugs targeting atrial-specific ion channels, Kv1.5 or Kir3.1/3.4, are being developed as new therapeutic strategies for atrial fibrillation. However, current preclinical studies carried out in non-cardiac cell lines or animal models may not accurately represent the physiology of a human cardiomyocyte (CM). In the current study, we tested whether human embryonic stem cell (hESC)-derived atrial CMs could predict atrial selectivity of pharmacological compounds. By modulating retinoic acid signaling during hESC differentiation, we generated atrial-like (hESC-atrial) and ventricular-like (hESC-ventricular) CMs. We found the expression of atrial-specific ion channel genes, KCNA5 (encoding Kv1.5) and KCNJ3 (encoding Kir 3.1), in hESC-atrial CMs and further demonstrated that these ion channel genes are regulated by COUP-TF transcription factors. Moreover, in response to multiple ion channel blocker, vernakalant, and Kv1.5 blocker, XEN-D0101, hESC-atrial but not hESC-ventricular CMs showed action potential (AP) prolongation due to a reduction in early repolarization. In hESC-atrial CMs, XEN-R0703, a novel Kir3.1/3.4 blocker restored the AP shortening caused by CCh. Neither CCh nor XEN-R0703 had an effect on hESC-ventricular CMs. In summary, we demonstrate that hESC-atrial CMs are a robust model for pre-clinical testing to assess atrial selectivity of novel antiarrhythmic drugs.
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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.