ArticleJournal of molecular and cellular cardiology2018
Functional and transcriptomic insights into pathogenesis of R9C phospholamban mutation using human induced pluripotent stem cell-derived cardiomyocytes.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Genotype-Dependent Effects of Mechanical Stretch and GATA4-Targeted Compound 3i-1262 in Cardiomyopathy Patient-Derived hiPSC-Cardiomyocytes.Basic & clinical pharmacology & toxicology · 2026Article
- Emerging Mechanisms and Therapeutic Strategies in Dilated Cardiomyopathy.Biomedicines · 2026Review
- Promoting Autophagy Mitigates Stress-Induced Remodeling in Patient iPSC-CMs with the Phospholamban R9C Mutation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Cardiac Organoids: A 3D Technology for Modeling Heart Development and Disease.Stem cell reviews and reports · 2022Review
- Suppression of lusitropy as a disease mechanism in cardiomyopathies.Frontiers in cardiovascular medicine · 2022Review
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- Review
- Engineered cardiac tissues: a novel in vitro model to investigate the pathophysiology of mouse diabetic cardiomyopathy.Acta pharmacologica Sinica · 2021Article
- Genetic Cardiomyopathies: The Lesson Learned from hiPSCs.Journal of clinical medicine · 2021Review
- Human-induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies.Cardiovascular research · 2021Review
- Association Study of Genetic Variants in Calcium Signaling-Related Genes With Cardiovascular Diseases.Frontiers in cell and developmental biology · 2021Article
- BET bromodomain proteins regulate transcriptional reprogramming in genetic dilated cardiomyopathy.JCI insight · 2020Article
- Trends and Limitations in the Assessment of the Contractile Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Patients With Dilated Cardiomyopathy.Frontiers in cardiovascular medicine · 2020Article
- Viral expression of a SERCA2a-activating PLB mutant improves calcium cycling and synchronicity in dilated cardiomyopathic hiPSC-CMs.Journal of molecular and cellular cardiology · 2020Article
- Advances in Stem Cell Modeling of Dystrophin-Associated Disease: Implications for the Wider World of Dilated Cardiomyopathy.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Dilated cardiomyopathy (DCM) can be caused by mutations in the cardiac protein phospholamban (PLN). We used CRISPR/Cas9 to insert the R9C PLN mutation at its endogenous locus into a human induced pluripotent stem cell (hiPSC) line from an individual with no cardiovascular disease. R9C PLN hiPSC-CMs display a blunted β-agonist response and defective calcium handling. In 3D human engineered cardiac tissues (hECTs), a blunted lusitropic response to β-adrenergic stimulation was observed with R9C PLN. hiPSC-CMs harboring the R9C PLN mutation showed activation of a hypertrophic phenotype, as evidenced by expression of hypertrophic markers and increased cell size and capacitance of cardiomyocytes. RNA-seq suggests that R9C PLN results in an altered metabolic state and profibrotic signaling, which was confirmed by gene expression analysis and picrosirius staining of R9C PLN hECTs. The expression of several miRNAs involved in fibrosis, hypertrophy, and cardiac metabolism were also perturbed in R9C PLN hiPSC-CMs. This study contributes to better understanding of the pathogenic mechanisms of the hereditary R9C PLN mutation in the context of human cardiomyocytes.
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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.