ArticleCirculation research2010
Neuregulin/ErbB signaling regulates cardiac subtype specification in differentiating human embryonic stem cells.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 232 citations in OpenAlex.
- Functional impairment of human resident cardiac stem cells by the cardiotoxic antineoplastic agent trastuzumab.Stem cells translational medicine · 2012Trial
- Targeted therapies in non-small cell lung cancer and their cardiovascular impact: mechanisms, clinical profiles, and strategies of management.Frontiers in pharmacology · 2026Review
- 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
- Promoting cardiomyocyte proliferation for myocardial regeneration in large mammals.Journal of molecular and cellular cardiology · 2024Review
- Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias.Frontiers in cardiovascular medicine · 2024Article
- Tissue-embedded stretchable nanoelectronics reveal endothelial cell-mediated electrical maturation of human 3D cardiac microtissues.Science advances · 2023Article
- Human-Induced Pluripotent Stem Cell-Based Differentiation of Cardiomyocyte Subtypes for Drug Discovery and Cell Therapy.Handbook of experimental pharmacology · 2023Article
- Cellular and Engineered Organoids for Cardiovascular Models.Circulation research · 2022Review
- A dualiScience · 2022Article
- Cell type determination for cardiac differentiation occurs soon after seeding of human-induced pluripotent stem cells.Genome biology · 2022Article
- Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements.International journal of molecular sciences · 2022Review
- Comprehensive transcriptome-wide analysis of spliceopathy correction of myotonic dystrophy using CRISPR-Cas9 in iPSCs-derived cardiomyocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Neuregulin-1, a potential therapeutic target for cardiac repair.Frontiers in pharmacology · 2022Review
- Cardiomyocyte Cell-Cycle Regulation in Neonatal Large Mammals: Single Nucleus RNA-Sequencing Data AnalysisFrontiers in bioengineering and biotechnology · 2022Article
- Review
- iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams.Biomedicines · 2021Review
- Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity in vitro.Cell systems · 2021Article
- Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies.International journal of molecular sciences · 2021Review
- The updated view on induced pluripotent stem cells for cardiovascular precision medicine.Pflugers Archiv : European journal of physiology · 2021Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleHuman embryonic stem cell-derived cardiomyocytes (hESC-CMs) exhibit either a "working" chamber or a nodal-like phenotype. To generate optimal hESC-CM preparations for eventual clinical application in cell-based therapies, we will need to control their differentiation into these specialized cardiac subtypes.
objectiveTo demonstrate intact neuregulin (NRG)-1β/ErbB signaling in hESC-CMs and test the hypothesis that this signaling pathway regulates cardiac subtype abundance in hESC-CM cultures. METHODS AND
resultsAll experiments used hESC-CM cultures generated using our recently reported directed differentiation protocol. To support subsequent action potential phenotyping approaches and provide a higher-throughput method of determining cardiac subtype, we first developed and validated a novel genetic label that identifies nodal-type hESC-CMs. Next, control hESC-CM preparations were compared to those differentiated in the presence of exogenous NRG-1β, an anti-NRG-1β neutralizing antibody, or the ErbB antagonist AG1478. We used 3 independent approaches to determine the ratio of cardiac subtypes in the resultant populations: direct action potential phenotyping under current-clamp, activation of the aforementioned genetic label, and subtype-specific marker expression by RT-PCR. Using all 3 end points, we found that inhibition of NRG-1β/ErbB signaling greatly enhanced the proportion of cells showing the nodal phenotype.
conclusionsNRG-1β/ErbB signaling regulates the ratio of nodal- to working-type cells in differentiating hESC-CM cultures and presumably functions similarly during early human heart development. We speculate that, by manipulating NRG-1β/ErbB signaling, it will be possible to generate preparations of enriched working-type myocytes for infarct repair, or, conversely, nodal cells for potential use in a biological pacemaker.
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Registered trials
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