Aberrant genomic imprinting in rhesus monkey embryonic stem cells

Akihisa Fujimoto, Shoukhrat M. Mitalipov, Hung Chih Kuo, Don P. Wolf

    Research output: Contribution to journalArticle

    27 Scopus citations

    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 cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs 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 ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.

    Original languageEnglish (US)
    Pages (from-to)595-603
    Number of pages9
    JournalStem Cells
    Volume24
    Issue number3
    DOIs
    StatePublished - Mar 1 2006

    Keywords

    • Embryonic stem cells
    • Embryos
    • Imprinting
    • Rhesus monkey

    ASJC Scopus subject areas

    • Molecular Medicine
    • Developmental Biology
    • Cell Biology

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