Telephone: 61-7-33463894; Fax: 61-7-33463973
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 26 OCT 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 10, pages 1782–1793, October 2010
How to Cite
Chung, T.-L., Turner, J. P., Thaker, N. Y., Kolle, G., Cooper-White, J. J., Grimmond, S. M., Pera, M. F. and Wolvetang, E. J. (2010), Ascorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells. STEM CELLS, 28: 1782–1793. doi: 10.1002/stem.500
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.
- Issue published online: 26 OCT 2010
- Article first published online: 26 OCT 2010
- Accepted manuscript online: 16 AUG 2010 12:00AM EST
- Manuscript Accepted: 9 AUG 2010
- Manuscript Received: 24 FEB 2010
- Human embryonic stem cells;
- Epigenetic changes;
- Culture adaptation
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