329 Modeling and Rescue of PLN-R14del Cardiomyopathy Phenotype in Human iPSC-Derived Cardiac Spheroids 12 REFERENCES 1. van der Zwaag, P. A. et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur. J. Heart Fail. 14, 1199–1207 (2012). 2. MacLennan, D. H. & Kranias, E. G. Phospholamban: a crucial regulator of cardiac contractility. Nat. Rev. Mol. Cell Biol. 4, 566–577 (2003). 3. Dridi, H. et al. Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target. Nat. Rev. Cardiol. 17, 732–747 (2020). 4. Bers, D. M. & Bridge, J. H. Relaxation of rabbit ventricular muscle by Na-Ca exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity. Circ. Res. 65, 334–342 (1989). 5. van der Voorn, S. M. et al. Exploring the Correlation Between Fibrosis Biomarkers and Clinical Disease Severity in PLN p.Arg14del Patients. Front Cardiovasc Med 8, 802998 (2021). 6. Regnier, M. & Childers, M. Familial Cardiomyopathies: Methods and Protocols. (Springer Nature, 2023). 7. Verstraelen, T. E. et al. Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriersreaching the frontiers of individual risk prediction. Eur. Heart J. 42, (2021). 8. Maione, A. S. et al. Fibrosis in Arrhythmogenic Cardiomyopathy: The Phantom Thread in the Fibro-Adipose Tissue. Front. Physiol. 11, 279 (2020). 9. Haghighi, K. et al. A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy. Proc. Natl. Acad. Sci. U. S. A. 103, (2006). 10. Te Rijdt, W. P. et al. Phospholamban p.Arg14del cardiomyopathy is characterized by phospholamban aggregates, aggresomes, and autophagic degradation. Histopathology 69, 542–550 (2016). 11. Sepehrkhouy, S. et al. Distinct fibrosis pattern in desmosomal and phospholamban mutation carriers in hereditary cardiomyopathies. Heart Rhythm 14, (2017). 12. Eijgenraam, T. R. et al. Protein Aggregation Is an Early Manifestation of Phospholamban p.(Arg14del)-Related Cardiomyopathy: Development of PLN-R14del-Related Cardiomyopathy. Circ. Heart Fail. 14, e008532 (2021). 13. Feyen, D. A. M. et al. Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy. Circulation 144, 382–392 (2021). 14. Cuello, F. et al. Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Arg14del mutation. EMBO Mol. Med. 13, e13074 (2021). 15. Harakalova, M. et al. Transcriptional regulation profiling reveals PPARA-mediated fatty acid oxidation as a novel therapeutic target in phospholamban R14del cardiomyopathy. (2022) doi:10.21203/rs.3.rs-1902254/v1. 16. Karakikes, I. et al. Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy. Nat. Commun. 6, 6955 (2015). 17. Yan, Y. et al. Cell population balance of cardiovascular spheroids derived from human induced pluripotent stem cells. Sci. Rep. 9, (2019). 18. Scalise, M. et al. From Spheroids to Organoids: The Next Generation of Model Systems of Human Cardiac Regeneration in a Dish. Int. J. Mol. Sci. 22, (2021). 19. Giacomelli, E. et al. Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease. Cell Stem Cell 26, (2020). 20. Lee, C. et al. Generation of three iPSC lines from dilated cardiomyopathy patients carrying a pathogenic LMNA variant. Stem Cell Res. 59, 102638 (2022). 21. Lian, X. et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl. Acad. Sci. U. S. A. 109, (2012). 22. Zhang, J. et al. Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors. Nat. Commun. 10, 2238 (2019). 23. Maas, R. G. C. et al. Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids. J. Vis. Exp. (2023) doi:10.3791/64365. 24. Feyen, D. A. M. et al. Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes. Cell Rep. 32, 107925 (2020).
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