Loss of Genomic Imprinting in Mouse Parthenogenetic Embryonic Stem Cells

¹ Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8511, Japan.
² Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8511, Japan.; PRESTO, Japan Science and Technology Corporation (JST), Saitama 332-0012, Japan.
³ Educational Development, College of Arts and Sciences, the University of Tokyo, Tokyo 153-8902, Japan

^* To whom correspondence should be addressed. E-mail: ihatada{at}showa.gunma-u.ac.jp.

	Abstract

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 cell (PGES) chimeras are more normal in their tissue contribution of donor cells and body weight compared to 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 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 cells 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.