ArticleStem cell research & therapy2020
Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- ESRG maintains human pluripotent stem cell self-renewal by binding NPM1 to regulate BMP4 protein and TGF-β signaling pathway.Cell & bioscience · 2026Article
- Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies.International journal of molecular sciences · 2026Review
- Coordination of cardiogenesis in vivo and in vitro.Nature reviews. Molecular cell biology · 2026Review
- BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models.Nature communications · 2025Article
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway.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 · 2025Article
- Bioprinting approaches in cardiac tissue engineering to reproduce blood-pumping heart function.iScience · 2025Review
- Review
- Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping.Disease models & mechanisms · 2024Article
- A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells.Signal transduction and targeted therapy · 2024Article
- 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
- Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.Journal of pharmaceutical analysis · 2024Article
- Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes.Biologics : targets & therapy · 2024Article
- The sinoatrial node extracellular matrix promotes pacemaker phenotype and protects automaticity in engineered heart tissues from cyclic strain.Cell reports · 2023Article
- Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies.Muscles (Basel, Switzerland) · 2023Review
- Review
- Patient-specific induced pluripotent stem cell properties implicate CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBiological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it is essential to develop highly efficient strategies for enrichment of sinoatrial node-like cells (SANLCs) as seed cells for biological pacemakers. It has been reported that BMP, FGF, and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells. We aimed to investigate whether combined modulation of BMP, FGF, and RA signaling pathways could enrich the differentiation of SANLC from human pluripotent stem cell (hiPSC).
methodsDuring the differentiation process from human induced pluripotent stem cell to cardiomyocyte through small molecule-based temporal modulation of the Wnt signaling pathway, signaling of BMP, FGF, and RA was manipulated at cardiac mesoderm stage. qRT-PCR, immunofluorescence, flow cytometry, and whole cell patch clamp were used to identify the SANLC.
resultsqRT-PCR results showed that manipulating each one of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and retinoid acid (RA) signaling was effective for the upregulation of SANLC markers. Moreover, combined modulation of these three pathways displayed the best efficiency for the expression of SANLC markers, which was further confirmed at protein level using immunofluorescence and flow cytometry. Finally, the electrophysiological characteristics of upregulated SANLC were verified by patch clamp method.
conclusionAn efficient transgene-independent differentiation protocol for generating SANLC from hiPSC was developed, in which combined modulating BMP, FGF, and RA signaling at cardiac mesoderm stage generates SANLC at high efficiency. This may serve as a potential approach for biological pacemaker construction.
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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.