title: Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells.
abstract: OBJECTIVE
  Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.
  
  
  RESULTS
  To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for 'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.
  
  
  CONCLUSIONS
  Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Tchao
authors.affiliation: Center for Cellular and Systems Electrophysiology, Department of Physiology and Biophysics, SUNY, Buffalo, NY 14214, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Kaplan
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Mich-Basso
authors.affiliation: Center for Cellular and Systems Electrophysiology, Department of Physiology and Biophysics, SUNY, Buffalo, NY 14214, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lis
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Narmeen
authors.initials: N
authors.lastname: Hassan
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: London
authors.affiliation: Department of Obstetrics and Gynecology, SUNY, Buffalo, NY 14214, USA.
authors.forename: Glenna C L
authors.initials: GC
authors.lastname: Bett
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.affiliation: Center for Cellular and Systems Electrophysiology, Department of Physiology and Biophysics, SUNY, Buffalo, NY 14214, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Rasmusson
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA lyang@pitt.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
mesh_terms: D000200:Action Potentials; D000328:Adult; D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000235:genetics; D010641:Phenotype; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure; D059467:Transcriptome
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Cardiomyocyte; Heart; Hypertrophic cardiomyopathy; Induced pluripotent stem cells