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Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics
Article first published online: 26 OCT 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 10, pages 1848–1855, October 2010
How to Cite
Chung, T.-L., Brena, R. M., Kolle, G., Grimmond, S. M., Berman, B. P., Laird, P. W., Pera, M. F. and Wolvetang, E. J. (2010), Vitamin C Promotes Widespread Yet Specific DNA Demethylation of the Epigenome in Human Embryonic Stem Cells. STEM CELLS, 28: 1848–1855. doi: 10.1002/stem.493
Author contributions: T.-L.C.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; R.M.B.: conception and design, collection and/or assembly of data, and data analysis and interpretation; G.K.: conception and design, collection and/or assembly of data, microarray data analysis and interpretation; S.M.G.: conception and design, and financial support; B.P.B.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; P.W.L.: conception and design, and financial support; 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 4, 2010.
- Issue published online: 26 OCT 2010
- Article first published online: 26 OCT 2010
- Manuscript Accepted: 22 JUL 2010
- Manuscript Received: 11 MAR 2010
- Human embryonic stem cells;
- Epigenetic changes;
- DNA hypomethylation;
- CpG shores
Vitamin C (ascorbate) is a widely used medium supplement in embryonic stem cell culture. Here, we show that ascorbate causes widespread, consistent, and remarkably specific DNA demethylation of 1,847 genes in human embryonic stem cells (hESCs), including important stem cell genes, with a clear bias toward demethylation at CpG island boundaries. We show that a subset of these DNA demethylated genes displays concomitant gene expression changes and that the position of the demethylated CpGs relative to the transcription start site is correlated to such changes. We further show that the ascorbate-demethylated gene set not only overlaps with gene sets that have bivalent marks, but also with the gene sets that are demethylated during differentiation of hESCs and during reprogramming of fibroblasts to induced pluritotent stem cells (iPSCs). Our data thus identify a novel link between ascorbate-mediated signaling and specific epigenetic changes in hESCs that might impact on pluripotency and reprogramming pathways. STEM CELLS 2010;28:1848–1855