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Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy

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Abstract

Generation of patient-specific induced pluripotent stem cells (iPSCs) and their subsequent differentiation into cardiomyocytes opened new opportunities for studying pathogenesis of inherited cardiovascular diseases. One of these diseases is hypertrophic cardiomyopathy (HCM) for which no efficient therapy methods have been developed so far. In this study, the approach based on patient-specific iPSCs was applied to create a model of the disease. Genetic analysis of a hypertrophic cardiomyopathy patient revealed R326Q mutation in the MYBPC3 gene. iPSCs of the patient were generated and characterized. The cells were differentiated into cardiomyocytes together with the control iPSCs from a healthy donor. The patient’s iPSC-derived cardiomyocytes exhibited early HCM features, such as abnormal calcium handling and increased intracellular calcium concentration. Therefore, cardiomyocytes obtained by directed differentiation of iPSCs from the HCM patient can be used as a model system to study HCM pathogenesis.

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Abbreviations

DAPI:

4′,6-diamidino-2-phenylindole

HCM:

hypertrophic cardiomyopathy

iPSCs:

induced pluripotent stem cells

MLC2:

ventricular form of the myosin light chain 2

MNCs:

mononuclear cells

MYBPC3:

cardiac myosin-binding protein C

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Authors and Affiliations

  1. Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    E. V. Dementyeva, S. P. Medvedev, V. R. Kovalenko & S. M. Zakian

  2. Meshalkin National Medical Research Center, Ministry of Health of Russian Federation, 630055, Novosibirsk, Russia

    E. V. Dementyeva, S. P. Medvedev, V. R. Kovalenko, E. I. Kretov, E. A. Pokushalov & S. M. Zakian

  3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    E. V. Dementyeva, S. P. Medvedev, V. R. Kovalenko & S. M. Zakian

  4. Novosibirsk State University, 630090, Novosibirsk, Russia

    S. P. Medvedev, V. R. Kovalenko, Yu. V. Vyatkin & S. M. Zakian

  5. Novel Software Systems Ltd, 630090, Novosibirsk, Russia

    Yu. V. Vyatkin & D. N. Shtokalo

  6. Moscow Institute of Physics and Technology, 141701, Dolgoprudny, Moscow Region, Russia

    M. M. Slotvitsky

  7. A. P. Ershov Institute of Informatics Systems, 630090, Novosibirsk, Russia

    D. N. Shtokalo

Authors
  1. E. V. Dementyeva
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  2. S. P. Medvedev
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  3. V. R. Kovalenko
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  4. Yu. V. Vyatkin
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  5. E. I. Kretov
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  6. M. M. Slotvitsky
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  7. D. N. Shtokalo
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  8. E. A. Pokushalov
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  9. S. M. Zakian
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Corresponding author

Correspondence to E. V. Dementyeva.

Additional information

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 3, pp. 413–422.

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Dementyeva, E.V., Medvedev, S.P., Kovalenko, V.R. et al. Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy. Biochemistry Moscow 84, 291–298 (2019). https://doi.org/10.1134/S0006297919030118

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  • DOI: https://doi.org/10.1134/S0006297919030118

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