Patient-specific iPSC-derived cardiomyocytes reveal variable phenotypic severity of Brugada syndrome.

Humans Brugada Syndrome / genetics Induced Pluripotent Stem Cells Myocytes, Cardiac Arrhythmias, Cardiac / pathology Mutation Death, Sudden, Cardiac / pathology
Asymptomatic mutation carriers Brugada syndrome Calcium current SCN5A iPSC-CMs

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Sep 2023
Historique:
received: 04 11 2022
revised: 19 07 2023
accepted: 19 07 2023
medline: 18 9 2023
pubmed: 7 8 2023
entrez: 6 8 2023
Statut: ppublish

Résumé

Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).

Sections du résumé

BACKGROUND BACKGROUND
Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation.
METHODS METHODS
26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol.
FINDINGS RESULTS
D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na
INTERPRETATION CONCLUSIONS
Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca
FUNDING BACKGROUND
National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).

Identifiants

DOI: 10.1016/j.ebiom.2023.104741 PMID: 37544203 PMC: PMC10427992
pubmed: 37544203
pii: S2352-3964(23)00306-7
doi: 10.1016/j.ebiom.2023.104741
pmc: PMC10427992
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104741

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no conflict of interests.

Auteurs

Yaxun Sun (Y)

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

Jun Su (J)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Xiaochen Wang (X)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Jue Wang (J)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Fengfeng Guo (F)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Hangyuan Qiu (H)

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

Hangping Fan (H)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Dongsheng Cai (D)

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

Hao Wang (H)

Prenatal Diagnosis Center, Hangzhou Women's Hospital, Hangzhou, 310008, China.

Miao Lin (M)

Department of Cardiology, Wenzhou Central Hospital, 325000, Wenzhou, China.

Wei Wang (W)

Jiangxi Provincial Cardiovascular Disease Research Institute, Jiangxi Provincial People's Hospital, Nanchang, 330006, China.

Ye Feng (Y)

Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China.

Guosheng Fu (G)

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

Tingyu Gong (T)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China; Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, China.

Ping Liang (P)

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China; Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China. Electronic address: pingliang@zju.edu.cn.

Chenyang Jiang (C)

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: cyjiang@zju.edu.cn.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Maladies génétiques congénitales › Syndrome de Brugada › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Troubles du rythme cardiaque › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Patient-specific iPSC-derived cardiomyocytes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Mort › Mort subite › Mort subite cardiaque › Patient-specific iPSC-derived cardiomyocytes...