Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology

Genomic imprinting in primate embryos and embryonic stem cells

Shoukhrat M. Mitalipov
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Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. Email:

Reproduction, Fertility and Development 18(8) 817-821
Submitted: 7 May 2006  Accepted: 4 September 2006   Published: 22 November 2006


Embryonic stem (ES) cells hold promise for cell and tissue replacement approaches to treating human diseases. However, long-term in vitro culture and manipulations of ES cells may adversely affect their epigenetic integrity including imprinting. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. We demonstrated aberrant biallelic expression of IGF2 and H19 in several rhesus monkey ES cell lines while SNRPN and NDN were normally imprinted and expressed from the paternal allele. In contrast, expanded blastocyst-stage embryos, from which these ES cells were derived, exhibited normal paternal expression of IGF2 and maternal expression of H19. To test the possibility that aberrant methylation at an imprinting centre (IC) upstream of H19 accounts for the relaxed imprinting of IGF2 and H19, we performed comprehensive methylation analysis by investigating methylation profiles of CpG sites within the IGF2/H19 IC. Our results demonstrate abnormal hypermethylation within the IGF2/H19 IC in all analysed ES cell lines consistent with biallelic expression of these genes. Cellular overproliferation and tumour formation resulting from tissue or cell transplantation are potential problems that must be addressed before clinical trials of ES cell-based therapy are initiated.

Extra keywords: methylation, rhesus monkey.


I would like to conclude by acknowledging my colleagues, present and former members of the ONPRC Embryonic Stem Cell Program, Dr Don Wolf, Dr Akihisa Fujimoto, Dr Hung-Chih Kuo, Hathaitip Sritanaudomchai, Cathy Ramsey, Lisa Clepper, Michelle Sparman, Carrie Thomas and Darlene Pedersen for their contributions in these studies. These studies were supported by NIH grants RR-00163, HD-18185, RR-15159 and NS-41601.


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