Open AccessAscorbate Promotes Epigenetic Activation of CD30 in Human Embryonic Stem Cells
Author(s) -
Chung TungLiang,
Turner Jennifer P.,
Thaker Nilay Y.,
Kolle Gabriel,
CooperWhite Justin J.,
Grimmond Sean M.,
Pera Martin F.,
Wolvetang Ernst J.
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.500
Subject(s) - biology , epigenetics , transcriptome , embryonic stem cell , dna methylation , microbiology and biotechnology , stem cell , induced pluripotent stem cell , reprogramming , cellular differentiation , cell potency , cancer research , cell , genetics , gene expression , gene
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. S TEM C ELLS 2010;28:1782–1793