Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells§

Authors

  • Tung-Liang Chung,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
    2. Australian Stem Cell Centre, Melbourne, Victoria, Australia
    3. Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia
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  • Jennifer P. Turner,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
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  • Nilay Y. Thaker,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
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  • Gabriel Kolle,

    1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
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  • Justin J. Cooper-White,

    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
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  • Sean M. Grimmond,

    1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
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  • Martin F. Pera,

    1. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California, USA
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  • Ernst J. Wolvetang

    Corresponding author
    1. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
    • Australian Institute for Bioengineering and Nanotechnology (AIBN), Corner College and Cooper Rds (Bldg 75), The University of Queensland, Brisbane, Queensland 4072, Australia
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    • Telephone: 61-7-33463894; Fax: 61-7-33463973


  • Author contributions: T.-L.C.: overall planning and design, collection and/or assembly of data, and data analysis and interpretation, and manuscript writing; J.T.: conception and design, collection and/or assembly of data, and data analysis and interpretation; N.T.: collection and/or assembly of data, data analysis and interpretation; G.K.: conception and design, collection and/or assembly of data, microarray data analysis and interpretation, and manuscript writing; J.C.-W.: conception and design, and financial support; S.M.G.: conception and design; M.F.P.: conception and design, data analysis and interpretation, and manuscript writing; E.W.: overall planning and design, financial support, and provision of study material or patients, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS August 16, 2010.

Abstract

Human embryonic stem cells (hESCs) and induced pluripotent stem cells have the ability to adapt to various culture conditions. Phenotypic and epigenetic changes brought about by the culture conditions can, however, have significant impacts on their use in research and in clinical applications. Here, we show that diploid hESCs start to express CD30, a biomarker for malignant cells in Hodgkin's disease and embryonal carcinoma cells, when cultured in knockout serum replacement (KOSR)-based medium, but not in fetal calf serum containing medium. We identify the commonly used medium additive, ascorbate, as the sole medium component in KOSR responsible for CD30 induction. Our data show that this epigenetic activation of CD30 expression in hESCs by ascorbate occurs through a dramatic loss of DNA methylation of a CpG island in the CD30 promoter. Analysis of the phenotype and transcriptome of hESCs that overexpress the CD30 signaling domain reveals that CD30 signaling leads to inhibition of apoptosis, enhanced single-cell growth, and transcriptome changes that are associated with cell signaling, lipid metabolism, and tissue development. Collectively, our data show that hESC culture media that contain ascorbate trigger CD30 expression through an epigenetic mechanism and that this provides a survival advantage and transcriptome changes that may help adapt hESCs to in vitro culture conditions. STEM CELLS 2010;28:1782–1793

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