Aberrant genomic imprinting in rhesus monkey ES cells

¹ Oregon National Primate Research Center, Beaverton, Oregon; Academia Sinica, Taipei, Taiwan
² Oregon National Primate Research Center, Beaverton, Oregon

^* To whom correspondence should be addressed. E-mail: wolfd{at}ohsu.edu.

	Abstract

Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem (ES) cells and in clonally derived animals. Imprinted gene expression patterns in primate ES cells are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ES cells, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ES cell lines containing useful single nucleotide polymorphisms (SNPs) were subjected to PCR based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting while IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ES cells, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ES progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ES cell differentiation in vitro and on ESderived cell function in vivo after transplantation are unknown.