Aberrant genomic imprinting in rhesus monkey embryonic stem cells

被引:22
作者
Fujimoto, Akihisa
Mitalipov, Shoukhrat M.
Kuo, Hung-Chih
Wolf, Don P.
机构
[1] Oregon Hlth & Sci Univ, Div Reprod Sci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA
[2] Univ Tokyo, Fac Med, Dept Obstet & Gynecol, Tokyo 113, Japan
[3] Acad Sinica, Genom Res Ctr, Stem Cell Program, Inst Zool, Taipei 115, Taiwan
关键词
imprinting; embryonic stem cells; rhesus monkey e; mbryos;
D O I
10.1634/stemcells.2005-0301
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:595 / 603
页数:9
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