Friedreich’s ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency

DOI HANDLE Web Site PubMed 参考文献42件
  • Duncan E. Crombie
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
  • Claire L. Curl
    Department of Physiology, the University of Melbourne, Melbourne, Australia
  • Antonia JA Raaijmakers
    Department of Physiology, the University of Melbourne, Melbourne, Australia
  • Priyadharshini Sivakumaran
    O’Brien Institute Department, St Vincent Institute of Medical Research, Fitzroy, Australia
  • Tejal Kulkarni
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
  • Raymond CB Wong
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
  • Itsunari Minami
    Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
  • Marguerite V. Evans-Galea
    Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, & Department of Paediatrics, The University of Melbourne, Melbourne, Australia
  • Shiang Y. Lim
    Ophthalmology, Department of Surgery, the University of Melbourne, Melbourne, Australia
  • Lea Delbridge
    O’Brien Institute Department, St Vincent Institute of Medical Research, Fitzroy, Australia
  • Louise A. Corben
    Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, & Department of Paediatrics, The University of Melbourne, Melbourne, Australia
  • Mirella Dottori
    Centre for Neural Engineering & Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, Australia
  • Norio Nakatsuji
    Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
  • Ian A. Trounce
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
  • Alex W. Hewitt
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
  • Martin B. Delatycki
    Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, & Department of Paediatrics, The University of Melbourne, Melbourne, Australia
  • Martin F. Pera
    Department of Anatomy and Neurosciences, the University of Melbourne, Florey Neuroscience & Mental Health Institute, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
  • Alice Pébay
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

書誌事項

公開日
2017-05-30
資源種別
journal article
DOI
  • 10.18632/aging.101247
公開者
Impact Journals, LLC

説明

We sought to identify the impacts of Friedreich's ataxia (FRDA) on cardiomyocytes. FRDA is an autosomal recessive degenerative condition with neuronal and non-neuronal manifestations, the latter including progressive cardiomyopathy of the left ventricle, the leading cause of death in FRDA. Little is known about the cellular pathogenesis of FRDA in cardiomyocytes. Induced pluripotent stem cells (iPSCs) were derived from three FRDA individuals with characterized GAA repeats. The cells were differentiated into cardiomyocytes to assess phenotypes. FRDA iPSC- cardiomyocytes retained low levels of FRATAXIN (FXN) mRNA and protein. Electrophysiology revealed an increased variation of FRDA- cardiomyocyte beating rates which was prevented by addition of nifedipine, suggestive of a calcium handling deficiency. Finally, calcium imaging was performed and we identified small amplitude, diastolic and systolic calcium transients confirming a deficiency in calcium handling. We defined a robust FRDA cardiac-specific electrophysiological profile in patient-derived iPSCs which could be used for high throughput compound screening. This cell-specific signature will contribute to the identification and screening of novel treatments for this life-threatening disease.

収録刊行物

  • Aging

    Aging 9 (5), 1440-1452, 2017-05-30

    Impact Journals, LLC

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