Loss of genomic imprinting in mouse parthenogenetic embryonic stem cells

被引:35
|
作者
Horii, Takuro [1 ]
Kimura, Mika [1 ,2 ]
Morita, Sumiyo [1 ,2 ]
Nagao, Yasumitsu [3 ]
Hatada, Izuho [1 ,2 ]
机构
[1] Gunma Univ, Inst Mol & Cellular Regulat, Lab Genome Sci, Biosignal Genome Res Ctr, Gunma 3718511, Japan
[2] Japan Sci & Technol Corp, PRESTO, Saitama, Japan
[3] Univ Tokyo, Coll Arts & Sci, Tokyo 153, Japan
关键词
embryonic stem cells; epigenetics; imprinting; methylation; reprogramming;
D O I
10.1634/stemcells.2006-0635
中图分类号
Q813 [细胞工程];
学科分类号
摘要
In mammals, complementary contributions of both the maternal and the paternal genomes are required for normal development because of the parental-allele-specific modification of the genome, called genomic imprinting. Therefore, parthenogenetic embryos (PG) with two maternal genomes cannot develop to term, and PG chimeras show a restricted cell contribution of donor cells and reduced weight, although they can develop to term. On the other hand, parthenogenetic embryonic stem cells (PGES) chimeras are more normal in their tissue contribution of donor cells and body weight compared with PG chimeras. To elucidate the epigenetic mechanisms underlying this, we analyzed the imprint status in donor cells of PGES and PG chimeras. In somatic lineages, genomic imprinting was lost in some PGES chimeras, whereas those in PG chimeras were almost totally maintained. Moreover, loss of imprints correlated to the gene expression pattern of imprinted genes. Therefore, this loss of imprinting in PGES chimeras could improve the tissue contribution and body weight to a normal level. On the other hand, in germ lineages, both PGES and PG in chimeras showed normal erasure of imprints, indicating that the reprogramming in germ lineages is an inevitable event, regardless of the imprint status of primordial germ cells.
引用
收藏
页码:79 / 88
页数:10
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