Embryonic Stem Cells Epigenetically Stable

NEW YORK (Reuters Health) - Expression patterns of most genes remain normal in cultured human embryonic stem cells (hESCs), according to a new report in Nature Genetics, published online on May 1st. Therefore, "the epigenetic status of human embryo-derived pluripotent cells and their differentiated progeny would not be a barrier to their therapeutic use," the investigators conclude.

Previous research has shown that imprinted genes in cultured embryos from sheep and mice are subject to "perturbation," lead author Dr. Peter J. Rugg-Gunn from the Cambridge Institute for Medical Research and his colleagues in the UK explain. There has also been some suggestion that assisted reproduction is associated with human epigenetic disorders (see Reuters Health reports, January 15 and January 23, 2003).

To further investigate, the researchers cultured hESCs from in vitro-fertilized embryos and analyzed gene expression. For three genes that are paternally expressed, they observed "strict monoallelic expression in all samples." Three genes that are maternally expressed also showed continued monoallelic expression after up to 65 passages.

Only one group of cells, H9, demonstrated expression of previously silent alleles of the H19 gene after prolonged passage. But even in this cell line, expression of the paternally expressed insulin-like growth factor 2 remained stable.

Analysis of key imprinting control regions of differentially methylated regions (DMR) of two genes that normally have maternal specific germline methylation showed equal proportions of fully methylated and fully unmethylated DNA, "consistent with maintenance of normal differential methylation," as did the H19 DMR during initial passages.

However, high-passage, biallelic H9 cells did show an increase in methylation of some sequences of the H19 DMR.

"Discordance between methylation and expression means that both must be studied for a definitive assessment of epigenetic stability during human development," Dr. Rugg-Gunn and his colleagues note.

Source: Nat Genet 2005. [ Google search on this article ]

MeSH Headings: Alkylation : Biological Sciences : Biology : Chemistry : Chemistry, Organic : Genetics : Genetics, Biochemical : Health Occupations : Methylation : Microbiological Techniques : Investigative Techniques : Molecular Biology : Physical Sciences : Serial Passage : Technology : Technology, Industry, and Agriculture : Technology, Medical : Allied Health Occupations : DNA Methylation : etiology : genetics : physiology : Analytical, Diagnostic and Therapeutic Techniques and Equipment : Biological Sciences : Physical Sciences : Technology, Food and Beverages

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