New approach to analyze inherited arrhythmias using human iPS cells

使用人类 iPS 细胞分析遗传性心律失常的新方法

• 批准号: 24659387
• 负责人: KIMURA Takeshi
• 金额: $ 2.41万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659387/
• 关键词: 不整脈; 分子心臓病態学; 分子心臓病態度学

In this study, we investigated the disease causing mechanisms of inherited arrhythmias using human iPS cell derived cardiomyocytes; 1. We assessed the ultrastructural changes of hiPS-CMs during a one-year culture and demonstrated the ultrastructural sarcomeric maturation process. 2. We generated disease-specific iPS cells from a patient associated with catecholaminergic polymorphic ventricular tachycardia. The differentiated cardiomyocytes had an increased susceptibility to catecholamine-induced calcium waves indicating that the cells recapiturated the CPVT phenotype. 3. We generated iPS cells and conducted whole exome sequencing in a large family with an inherited arrhythmia (under analysis).

在这项研究中，我们利用人类iPS细胞衍生的心肌细胞研究了遗传性心律失常的致病机制；1. 我们在一年的培养过程中评估了hiPS-CMs的超微结构变化，并展示了超微结构的肌体成熟过程。2. 我们从一位与儿茶酚胺能多形性室性心动过速相关的患者身上产生了疾病特异性的iPS细胞。分化的心肌细胞对儿茶酚胺诱导的钙波的敏感性增加，表明细胞重现了CPVT表型。3. 我们产生了iPS细胞，并对一个遗传性心律失常的大家族进行了全外显子组测序（正在分析中）。

项目成果

Phenotype Variability in Patients Carrying KCNJ2 Mutations

携带 KCNJ2 突变的患者的表型变异

• DOI: 10.1161/circgenetics.111.962316
• 发表时间: 2012-06-01
• 期刊: CIRCULATION-CARDIOVASCULAR GENETICS
• 作者: Kimura, Hiromi;Zhou, Jun;Horie, Minoru
• 通讯作者: Horie, Minoru

Genetic Backgrounds in Patients with Early-Onset and Familial Atrial Fibrillation

早发型家族性房颤患者的遗传背景

• 发表时间: 2012
• 作者: Watanabe H;Nogami A;Ohkubo K;Kawata H;Hayashi Y;Ishikawa T;Makiyama T;Nagao S;Yagihara N;Takehara N;Kawamura Y;Sato A;Okamura K;Hosaka Y;Sato M;Fukae S;Chinushi M;Oda H;Okabe M;Kimura A;Maemura K;Watanabe;Kimura H;Watanabe H;佐々木 健一;Yimin Wuriyanghai;牧山武;佐々木健一;牧山武;鎌倉 令;鎌倉 令
• 通讯作者: 鎌倉 令

Phenotypic characteristics between SCN5A and LMNA mutation carriers in familial bradyarrhythmic disorders

家族性缓慢性心律失常疾病中 SCN5A 和 LMNA 突变携带者的表型特征

• 发表时间: 2012
• 作者: Watanabe H;Nogami A;Ohkubo K;Kawata H;Hayashi Y;Ishikawa T;Makiyama T;Nagao S;Yagihara N;Takehara N;Kawamura Y;Sato A;Okamura K;Hosaka Y;Sato M;Fukae S;Chinushi M;Oda H;Okabe M;Kimura A;Maemura K;Watanabe;Kimura H;Watanabe H;佐々木 健一;Yimin Wuriyanghai;牧山武;佐々木健一;牧山武;鎌倉 令;鎌倉 令;佐々木 健一;牧山武
• 通讯作者: 牧山武

Identification of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells using a Cardiac Specific Lentiviral Vector

使用心脏特异性慢病毒载体鉴定源自人诱导多能干细胞的心肌细胞

• 发表时间: 2013
• 作者: Watanabe H;Nogami A;Ohkubo K;Kawata H;Hayashi Y;Ishikawa T;Makiyama T;Nagao S;Yagihara N;Takehara N;Kawamura Y;Sato A;Okamura K;Hosaka Y;Sato M;Fukae S;Chinushi M;Oda H;Okabe M;Kimura A;Maemura K;Watanabe;Kimura H;Watanabe H;佐々木 健一;Yimin Wuriyanghai
• 通讯作者: Yimin Wuriyanghai

Ca2+ Imaging of Cardiomyocytes Differentiated from Human Induced Pluripotent Stem Cells in Catecholaminergic Polymorphic Ventricular Tachycardia

儿茶酚胺能多形性室性心动过速中人诱导多能干细胞分化的心肌细胞的 Ca2 成像

• 发表时间: 2013
• 作者: Watanabe H;Nogami A;Ohkubo K;Kawata H;Hayashi Y;Ishikawa T;Makiyama T;Nagao S;Yagihara N;Takehara N;Kawamura Y;Sato A;Okamura K;Hosaka Y;Sato M;Fukae S;Chinushi M;Oda H;Okabe M;Kimura A;Maemura K;Watanabe;Kimura H;Watanabe H;佐々木 健一;Yimin Wuriyanghai;牧山武;佐々木健一
• 通讯作者: 佐々木健一