Ascorbate promotes epigenetic activation of CD30 in human embryonic stem cells

Chung, Tung-Liang, Turner, Jennifer P., Thaker, Nilay Y., Kolle, Gabriel, Cooper-White, Justin J., Grimmond, Sean M., Pera, Martin F. and Wolvetang, Ernst J. (2010) Ascorbate promotes epigenetic activation of CD30 in human embryonic stem cells. Stem Cells, 28 10: 1782-1793. doi:10.1002/stem.500

Author Chung, Tung-Liang
Turner, Jennifer P.
Thaker, Nilay Y.
Kolle, Gabriel
Cooper-White, Justin J.
Grimmond, Sean M.
Pera, Martin F.
Wolvetang, Ernst J.
Title Ascorbate promotes epigenetic activation of CD30 in human embryonic stem cells
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1002/stem.500
Volume 28
Issue 10
Start page 1782
End page 1793
Total pages 12
Editor Miodrag Stojkovic
Martin J. Murphy
Place of publication Durham, NC., U.S.A.
Publisher Wiley-Blackwell and AlphaMed Press
Collection year 2011
Language eng
Formatted 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 pheno-type 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.
© AlphaMed Press.
Keyword Human embryonic stem cells
Epigenetic changes
Culture adaptation
Reed-sternberg cells
Kappa B activation
Long-term culture
Zinc-finger genes
Growth factor
Collagen hydroxylation
Glutathione depletion
Enhance expression
Cytokine receptor
Human blastocysts
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 32 times in Scopus Article | Citations
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Created: Sun, 05 Dec 2010, 00:00:39 EST