The effects of culture on genomic imprinting profiles in human embryonic and fetal mesenchymal stem cells

Frost, Jennifer M., Monk, Dave, Moschidou, Dafni, Guillot, Pascale V., Stanier, Philip, Minger, Stephen L., Fisk, Nicholas M., Moore, Harry D. and Moore, Gudrun E. (2011) The effects of culture on genomic imprinting profiles in human embryonic and fetal mesenchymal stem cells. Epigenetics, 6 1: 52-62. doi:10.4161/epi.6.1.13361


Author Frost, Jennifer M.
Monk, Dave
Moschidou, Dafni
Guillot, Pascale V.
Stanier, Philip
Minger, Stephen L.
Fisk, Nicholas M.
Moore, Harry D.
Moore, Gudrun E.
Title The effects of culture on genomic imprinting profiles in human embryonic and fetal mesenchymal stem cells
Journal name Epigenetics   Check publisher's open access policy
ISSN 1559-2294
1559-2308
Publication date 2011-01
Sub-type Article (original research)
DOI 10.4161/epi.6.1.13361
Volume 6
Issue 1
Start page 52
End page 62
Total pages 11
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Collection year 2012
Language eng
Formatted abstract
Human embryonic stem (hES) cells and fetal mesenchymal stem cells (fMSC) offer great potential for regenerative therapy strategies. It is therefore important to characterise the properties of these cells in vitro. One major way the environment impacts on cellular physiology is through changes to epigenetic mechanisms. Genes subject to epigenetic regulation via genomic imprinting have been characterised extensively. The integrity of imprinted gene expression therefore provides a measurable index for epigenetic stability. Allelic expression of 26 imprinted genes and DNA methylation at associated differentially methylated regions (DMRs) was measured in fMSC and hES cell lines. Both cell types exhibited monoallelic expression of 13 imprinted genes, biallelic expression of six imprinted genes, and there were seven genes that differed in allelic expression between cell lines. fMSCs exhibited the differential DNA methylation patterns associated with imprinted expression. This was unexpected given that gene expression of several imprinted genes was biallelic. However, in hES cells, differential methylation was perturbed. These atypical methylation patterns did not correlate with allelic expression. Our results suggest that regardless of stem cell origin, in vitro culture affects the integrity of imprinted gene expression in human cells. We identify biallelic and variably expressed genes that may inform on overall epigenetic stability. As differential methylation did not correlate with imprinted expression changes we propose that other epigenetic effectors are adversely influenced by the in vitro environment. Since DMR integrity was maintained in fMSC but not hES cells, we postulate that specific hES cell derivation and culturing practices result in changes in methylation at DMRs.
Keyword Genomic imprinting
Embryonic stem cells
Mesenchymal stem cells
Differentiation
Methylation
Epigenetic stability
Dna methylation
Control region
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
UQ Centre for Clinical Research Publications
Official 2012 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 24 times in Scopus Article | Citations
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Created: Sun, 06 Feb 2011, 00:09:28 EST