Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain-of-function mutations in the cardiac ryanodine receptor gene (RYR2) account f...

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Autores: Arslanova, Alia, Shafaattalab, Sanam, Ye, Kevin, Asghari, Parisa, Lin, Lisa, Kim, BaRun, Roston, Thomas M., Hove-Madsen, Leif, Petegem, Filip van, Sanatani, Shubhayan, Moore, Edwin, Lynn, Francis C., Søndergaard, Mads, Luo, Yonglun, Chen, S. R. Wayne, Tibbits, Glen F.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/261082
Acceso en línea:http://hdl.handle.net/10261/261082
Access Level:acceso abierto
Palabra clave:Catecholaminergic polymorphic ventricular tachycardia
Diseasemodeling
Human induced pluripotent stem cells
Inherited arrhythmia
Ryanodine receptor
Sudden cardiac death
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spelling Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular TachycardiaArslanova, AliaShafaattalab, SanamYe, KevinAsghari, ParisaLin, LisaKim, BaRunRoston, Thomas M.Hove-Madsen, LeifPetegem, Filip vanSanatani, ShubhayanMoore, EdwinLynn, Francis C.Søndergaard, MadsLuo, YonglunChen, S. R. WayneTibbits, Glen F.Catecholaminergic polymorphic ventricular tachycardiaDiseasemodelingHuman induced pluripotent stem cellsInherited arrhythmiaRyanodine receptorSudden cardiac deathCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain-of-function mutations in the cardiac ryanodine receptor gene (RYR2) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca) homeostasis particularly during the periods of β-adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well-established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT-causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease-specific cell lines from healthy and diseased patient-derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC-based model of CPVT in order to recapitulate the disease phenotype in vitro and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC-derived cardiomyocytes. © 2021 Wiley Periodicals LLC.The authors gratefully acknowledge financial support from the Stem Cell Network(FY21/ACCT2-13 to GFT); the Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health (GR020601 toGFT and FVP); and the Mining for Miraclesfund raising on behalf of the BC Children’s Hospital Foundation (to G.F.T., S.S., and F.L.).Peer reviewedJohn Wiley & SonsStem Cell NetworkCanadian Institutes of Health ResearchBC Children's Hospital FoundationConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPostprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/261082reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1002/cpz1.320Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2610822026-05-22T06:33:51Z
dc.title.none.fl_str_mv Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
title Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
spellingShingle Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
Arslanova, Alia
Catecholaminergic polymorphic ventricular tachycardia
Diseasemodeling
Human induced pluripotent stem cells
Inherited arrhythmia
Ryanodine receptor
Sudden cardiac death
title_short Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
title_full Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
title_fullStr Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
title_full_unstemmed Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
title_sort Using hiPSC-CMs to Examine Mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia
dc.creator.none.fl_str_mv Arslanova, Alia
Shafaattalab, Sanam
Ye, Kevin
Asghari, Parisa
Lin, Lisa
Kim, BaRun
Roston, Thomas M.
Hove-Madsen, Leif
Petegem, Filip van
Sanatani, Shubhayan
Moore, Edwin
Lynn, Francis C.
Søndergaard, Mads
Luo, Yonglun
Chen, S. R. Wayne
Tibbits, Glen F.
author Arslanova, Alia
author_facet Arslanova, Alia
Shafaattalab, Sanam
Ye, Kevin
Asghari, Parisa
Lin, Lisa
Kim, BaRun
Roston, Thomas M.
Hove-Madsen, Leif
Petegem, Filip van
Sanatani, Shubhayan
Moore, Edwin
Lynn, Francis C.
Søndergaard, Mads
Luo, Yonglun
Chen, S. R. Wayne
Tibbits, Glen F.
author_role author
author2 Shafaattalab, Sanam
Ye, Kevin
Asghari, Parisa
Lin, Lisa
Kim, BaRun
Roston, Thomas M.
Hove-Madsen, Leif
Petegem, Filip van
Sanatani, Shubhayan
Moore, Edwin
Lynn, Francis C.
Søndergaard, Mads
Luo, Yonglun
Chen, S. R. Wayne
Tibbits, Glen F.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Stem Cell Network
Canadian Institutes of Health Research
BC Children's Hospital Foundation
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Catecholaminergic polymorphic ventricular tachycardia
Diseasemodeling
Human induced pluripotent stem cells
Inherited arrhythmia
Ryanodine receptor
Sudden cardiac death
topic Catecholaminergic polymorphic ventricular tachycardia
Diseasemodeling
Human induced pluripotent stem cells
Inherited arrhythmia
Ryanodine receptor
Sudden cardiac death
description Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac arrhythmia condition, triggered by physical or acute emotional stress, that predominantly expresses early in life. Gain-of-function mutations in the cardiac ryanodine receptor gene (RYR2) account for the majority of CPVT cases, causing substantial disruption of intracellular calcium (Ca) homeostasis particularly during the periods of β-adrenergic receptor stimulation. However, the highly variable penetrance, patient outcomes, and drug responses observed in clinical practice remain unexplained, even for patients with well-established founder RyR2 mutations. Therefore, investigation of the electrophysiological consequences of CPVT-causing RyR2 mutations is crucial to better understand the pathophysiology of the disease. The development of strategies for reprogramming human somatic cells to human induced pluripotent stem cells (hiPSCs) has provided a unique opportunity to study inherited arrhythmias, due to the ability of hiPSCs to differentiate down a cardiac lineage. Employment of genome editing enables generation of disease-specific cell lines from healthy and diseased patient-derived hiPSCs, which subsequently can be differentiated into cardiomyocytes. This paper describes the means for establishing an hiPSC-based model of CPVT in order to recapitulate the disease phenotype in vitro and investigate underlying pathophysiological mechanisms. The framework of this approach has the potential to contribute to disease modeling and personalized medicine using hiPSC-derived cardiomyocytes. © 2021 Wiley Periodicals LLC.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/261082
url http://hdl.handle.net/10261/261082
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1002/cpz1.320
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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