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First published online October 25, 2007
Stem Cells Vol. 26 No. 1 January 2008, pp. 79 -88
doi:10.1634/stemcells.2006-0635; www.StemCells.com
© 2008 AlphaMed Press

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EMBRYONIC STEM CELLS

Loss of Genomic Imprinting in Mouse Parthenogenetic Embryonic Stem Cells

Takuro Horiia, Mika Kimuraa,b, Sumiyo Moritaa,b, Yasumitsu Nagaoc, Izuho Hatadaa,b

aLaboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan;
bPRESTO, Japan Science and Technology Corporation, Saitama, Japan;
cEducational Development, College of Arts and Sciences, University of Tokyo, Tokyo, Japan

Key Words. Embryonic stem cells • Epigenetics • Imprinting • Methylation • Reprogramming

Correspondence: Izuho Hatada, Ph.D., Biosignal Genome Resource Center, Laboratory of Genome Science, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Telephone: 81-27-220-8057; Fax: 81-27-220-8110; e-mail: ihatada{at}showa.gunma-u.ac.jp

Received October 5, 2006; accepted for publication October 18, 2007.
First published online in STEM CELLS EXPRESS   October 25, 2007.



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.

Disclosure of potential conflicts of interest is found at the end of this article.







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