ArticleStem cell reports2022
Modeling reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency using isogenic iPS cell-derived cardiomyocytes.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Tackling non-canonical splicing in arrhythmogenic cardiomyopathy to reduce the uncertain significance variants burden.Journal of translational medicine · 2026Article
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- Disease models and AAV therapies ofMolecular therapy. Advances · 2026Review
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Consequences of Right Heart Disease for Cardiac Electrophysiology and Arrhythmias: Cellular and Structural Mechanisms.CJC open · 2025Review
- Genetic Variants in Genes Related to Lung Function and Interstitial Lung Diseases Are Associated with Worse Outcomes in Severe COVID-19 and Lung Performance in the Post-COVID-19 Condition.International journal of molecular sciences · 2025Article
- Four cardiomyopathy patients with a heterozygous DSG2 p.Arg119Ter variant.Human genome variation · 2024Article
- Exploring the Therapeutic Potential of Gene Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy.Biomedicines · 2024Review
- Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.Research square · 2023Article
- SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2023Article
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Spatiotemporal cell junction assembly in human iPSC-CM models of arrhythmogenic cardiomyopathy.Stem cell reports · 2023Article
- Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy.European heart journal open · 2023Article
- Review
- Modeling Reduced Contractility and Stiffness Using iPSC-Derived Cardiomyocytes Generated From Female Becker Muscular Dystrophy Carrier.JACC. Basic to translational science · 2023Article
- Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes.World journal of stem cells · 2023Review
- The Exciting Realities and Possibilities of iPS-Derived Cardiomyocytes.Bioengineering (Basel, Switzerland) · 2023Review
- Therapeutic efficacy of AAV-mediated restoration of PKP2 in arrhythmogenic cardiomyopathy.Nature cardiovascular research · 2023Article
- Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells.Frontiers in physiology · 2023Review
- Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes.Computational and structural biotechnology journal · 2023Article
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in PKP2, which encodes plakophilin-2, cause arrhythmogenic cardiomyopathy (AC). Restoration of deficient molecules can serve as upstream therapy, thereby requiring a human model that recapitulates disease pathology and provides distinct readouts in phenotypic analysis for proof of concept for gene replacement therapy. Here, we generated isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with precisely adjusted expression of plakophilin-2 from a patient with AC carrying a heterozygous frameshift PKP2 mutation. After monolayer differentiation, plakophilin-2 deficiency led to reduced contractility, disrupted intercalated disc structures, and impaired desmosome assembly in iPSC-CMs. Allele-specific fluorescent labeling of endogenous DSG2 encoding desmoglein-2 in the generated isogenic lines enabled real-time desmosome-imaging under an adjusted dose of plakophilin-2. Adeno-associated virus-mediated gene replacement of PKP2 recovered contractility and restored desmosome assembly, which was sequentially captured by desmosome-imaging in plakophilin-2-deficient iPSC-CMs. Our isogenic set of iPSC-CMs recapitulates AC pathology and provides a rapid and convenient cellular platform for therapeutic development.
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