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Mol. Hum. Reprod. Advance Access originally published online on March 18, 2009
Molecular Human Reproduction 2009 15(6):345-353; doi:10.1093/molehr/gap023
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Comparative methylation profiles and telomerase biology of mouse multipotent adult germline stem cells and embryonic stem cells

Ulrich Zechner1,3,{dagger}, Jessica Nolte2,{dagger}, Marieke Wolf1, Katayoon Shirneshan2, Nady El Hajj1, Daniela Weise1, Britta Kaltwasser2, Athanasios Zovoilis2, Thomas Haaf1 and Wolfgang Engel2

1 Institute of Human Genetics, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55101 Mainz, Germany 2 Institute of Human Genetics, Georg-August-University Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany

3 Correspondence address. Tel: +49-6131-17-5850; Fax: +49-6131-17-5689; E-mail: zechner{at}humgen.klinik.uni-mainz.de

Recently, several groups described the isolation of mouse spermatogonial stem cells (SSCs) and their potential to develop to embryonic stem cell (ESC)-like cells, so-called multipotent germline stem cells (mGSCs). We were the first to derive such mGSCs from SSCs isolated from adult mouse testis and, therefore, called these mGSCs multipotent adult germline stem cells (maGSCs). Here, we comparatively analyzed gene-specific and global DNA methylation profiles as well as the telomerase biology of several maGSC and male ESC lines. We show that undifferentiated maGSCs are very similar to undifferentiated male ESCs with regard to global DNA methylation, methylation of pluripotency marker gene loci, telomerase activity and telomere length. Imprinted gene methylation levels were generally lower in undifferentiated maGSCs than in undifferentiated male ESCs, but, compared with undifferentiated mGSCs derived by other groups, more similar to those of male ESCs. Differentiation of maGSCs increased the methylation of three of the four analyzed imprinted genes to almost somatic methylation patterns, but dramatically decreased global DNA methylation. Our findings further substantiate the pluripotency of maGSCs and their potential for regenerative medicine.

Key words: genome-wide methylation/imprinted genes/multipotent adult germline stem cells/pluripotency marker genes/telomerase biology

{dagger} These two authors contributed equally to this work.

Submitted on January 13, 2009; resubmitted on March 12, 2009; accepted on March 16, 2009.


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