New approach to analyze inherited arrhythmias using human iPS cells

• Project/Area Number: 24659387
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KIMURA Takeshi 京都大学, 医学研究科, 教授 (80359786)
• Research Collaborator: MAKIYAMA Takeru 京都大学, 医学研究科, 助教 (30528302)
• Project Period (FY): 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 不整脈 / 分子心臓病態学 / 分子心臓病態度学

Research Abstract

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).

Research Products

• [Journal Article] Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture (2013)
  • Author(s): Kamakura T, Makiyama T, Sasaki K, Yoshida Y, Wuriyanghai Y, Chen J, Hattori T, Ohno S, Kita T, Horie M, Yamanaka S, Kimura T
  • Journal Title: Circ J
  • NAID: 10031151395
• [Journal Article] Long-Term Follow-Up of a Pediatric Cohort With Short QT Syndrome (2013)
  • Author(s): Villafane J, Atallah J, Gollob MH, Maury P, Wolpert C, Gebauer R, Watanabe H, Horie M, Anttonen O, Kannankeril P, Faulknier B, Bleiz J, Makiyama T, Shimizu W, Hamilton R, Young ML
  • Journal Title: J Am Coll Cardiol
• [Journal Article] Ultrastructural Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Long-Term Culture (2013)
  • Author(s): Kamakura T
  • Journal Title: Circ J Volume: 77 Pages: 1307-14
  • Peer Reviewed
• [Journal Article] Long-Term Follow-Up of a Pediatric Cohort With Short QT Syndrome (2013)
  • Author(s): Villafarie J
  • Journal Title: J Am Coll Cardiol Volume: 61 Pages: 1183-91
  • Peer Reviewed
• [Journal Article] A. Novel SCN3B Mutation Associated With Brugada Syndrome Affects Intracellular Trafficking and Function of Nav1.5 (2013)
  • Author(s): Ishikawa T
  • Journal Title: Circ J Volume: 77 Pages: 959-67
  • Peer Reviewed
• [Journal Article] Novel SCN3B Mutation Associated With Brugada Syndrome Affects Intracellular Trafficking and Function of Nav1.5 (2012)
  • Author(s): Ishikawa T, Takahashi N, Ohno S, Sakurada H, Nakamura K, On YK, Park JE, Makiyama T, Horie M, Arimura T, Makita N, Kimura A
  • Journal Title: Circ J
• [Journal Article] A novel gain-of-function KCNJ2 mutation associated with short QT syndrome impairs inward rectification of Kir2.1 currents. (2012)
  • Author(s): Hattori T, Makiyama T, Akao M, Ehara E, Ohno S, Iguchi M, Nishio Y, Sasaki K, Itoh H, Yokode M, Kita T, Horie M, Kimura T
  • Journal Title: Cardiovasc Res Volume: 93(4) Pages: 666-73
• [Journal Article] Phenotype variability in patients carrying KCNJ2 mutations. (2012)
  • Author(s): Kimura H, Zhou J, Kawamura M, Itoh H, Mizusawa Y, Ding WG, Wu J, Ohno S, Makiyama T, Miyamoto A, Naiki N, Wang Q, Xie Y, Suzuki T, Tateno S, Nakamura Y, Zang WJ, Ito M, Matsuura H, Horie M
  • Journal Title: Circ Cardiovasc Genet. Volume: 5(3) Pages: 344-53
• [Journal Article] Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization. (2012)
  • Author(s): 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
  • Journal Title: Int J Cardiol Volume: 159(3) Pages: 238-40
• [Journal Article] Phenotype variability in patients carrying KCNJ2 mutations (2012)
  • Author(s): Kimura H
  • Journal Title: Circ Cardiovasc Genet Volume: 5 Pages: 344-53
  • Peer Reviewed
• [Journal Article] Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization (2012)
  • Author(s): Watanabe H
  • Journal Title: Int J Cardiol Volume: 159 Pages: 238-40
  • Peer Reviewed
• [Presentation] Disease Modeling in Human Induced Pluripotent Stem Cells-Catecholaminergic Polymorphic Ventricular Tachycardia- (2013)
  • Author(s): 牧山武
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] O Ca2+ Imaging of Cardiomyocytes Differentiated from Human Induced Pluripotent Stem Cells in Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 佐々木 健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] One Year Assessment ofIon Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2013)
  • Author(s): 佐々木 健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Identification of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells using a Cardiac Specific Lentiviral Vector (2013)
  • Author(s): Yimin Wuriyanghai
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Disease Modeling in Human Induced Pluripotent Stem Cells -Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 牧山武
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Ca2+ Imaging of Cardiomyocytes Differentiated from Human Induced Pluripotent Stem Cells in Catecholaminergic Polymorphic Ventricular Tachycardia (2013)
  • Author(s): 佐々木健一
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Phenotypic characteristics between SCN5A and LMNA mutation carriers in familial bradyarrhythmic disorders. (2012)
  • Author(s): 牧山武
  • Organizer: The 5thAsia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One-year assessment of the ultrastructural changes of human induced pluripotent stem cell-derived cardiomyocytes (2012)
  • Author(s): 鎌倉 令
  • Organizer: European Society of Cardiology (ESC) Congress
  • Place of Presentation: Munich,Germany
• [Presentation] Genetic Backgrounds in Patients with Early-Onset and Familial Atrial Fibrillation (2012)
  • Author(s): 鎌倉 令
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One Year Assessment ofIon Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2012)
  • Author(s): 佐々木 健一
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Phenotypic characteristics between SCN5A and LMNA mutation carriers in familial bradyarrhythmic disorders (2012)
  • Author(s): 牧山武
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan
• [Presentation] One-year assessment of the ultrastructural changes of human induced pluripotent stem cell-derived cardiomyocytes (2012)
  • Author(s): 鎌倉令
  • Organizer: European Society of Cardiology (ESC) Congress
  • Place of Presentation: Munich, Germany
• [Presentation] One Year Assessment of Ion Channel Gene Expression in Cardiomyocytes derived from Human Induced Pluripotent Stem Cells (2012)
  • Author(s): 佐々木健一
  • Organizer: The 5th Asia-Pacific Heart Rhythm Society (APHRS) Scientific Session
  • Place of Presentation: Taipei, Taiwan