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Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast

Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast

• Otx2 binds to the promoter/enhancer region of Oct4, Sox2, and Nanog in ESCs and EpiSCs • Otx2 binding to the Nanog promoter helps maintain the integrity of ESC compartments • Loss of this Otx2-binding site induces primed-like features in ESCs • Otx2 regulation of Nanog contributes to ICM differentiation of the epiblast Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we uncover a role for Otx2 in the control of the naive pluripotent state. We analyzed Otx2-binding activity in ESCs and EpiSCs and identified Nanog, Oct4, and Sox2 as direct targets. To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in vivo, predisposing ICM differentiation to epiblast. Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.

CNR Science 22 Jun 2016
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K2 and Baltoro cleaned from 8 tonnes of waste

K2 and Baltoro cleaned from 8 tonnes of waste

8,000 kilos of waste (paper, plastic, cans, glass and toxic materials) have been carried down from the Baltoro glacier over the past weeks.Over 2,000 kilos have already been burned. These are the first results of the "Keep Baltoro Clean" campaign, organized by the EvK2Cnr Committee and the Pakistan Alpine Club in the framework of Karakorum Trust project. The operation is aimed at cleaning up from waste the Baltoro glacier, the base camps and the higher camps of the expeditions climbing the surrounding mountains.

CNR Environment 28 Jul 2009
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