2013
DOI: 10.1089/scd.2012.0256
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The Combination of Inhibitors of FGF/MEK/Erk and GSK3β Signaling Increases the Number of OCT3/4- and NANOG-Positive Cells in the Human Inner Cell Mass, But Does Not Improve Stem Cell Derivation

Abstract: In embryonic stem cell culture, small molecules can be used to alter key signaling pathways to promote self-renewal and inhibit differentiation. In mice, small-molecule inhibition of both the FGF/MEK/Erk and the GSK3b pathways during preimplantation development suppresses hypoblast formation, and this results in more pluripotent cells of the inner cell mass (ICM). In this study, we evaluated the effects of different small-molecule inhibitors of the FGF/ MEK/Erk and GSK3b pathway on embryo preimplantation devel… Show more

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Cited by 29 publications
(21 citation statements)
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References 38 publications
(63 reference statements)
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“…Even under seemingly identical conditions, we still observed hypoblast cells in embryos although their number was significantly reduced compared with controls. Our results are in line with what was reported in human embryos cultured in 2i [9]. Therefore, we propose that additional mechanisms governing hypoblast formation events do exist besides FGF signaling, which need to be further investigated.…”
Section: Discussionsupporting
confidence: 92%
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“…Even under seemingly identical conditions, we still observed hypoblast cells in embryos although their number was significantly reduced compared with controls. Our results are in line with what was reported in human embryos cultured in 2i [9]. Therefore, we propose that additional mechanisms governing hypoblast formation events do exist besides FGF signaling, which need to be further investigated.…”
Section: Discussionsupporting
confidence: 92%
“…The increased number of epiblast cells and decreased number of hypoblast cells in embryos cultured in the presence of an FGF inhibitor is neither the result of selective proliferation of epiblast lineage nor the outcome of apoptosis of the hypoblast lineage but is due to selective lineage choice in the presence of these inhibitors [5]. Similarly, it was shown that 2i supplementation significantly increased the number of epiblast cells in human embryos [9]. In contrast to mice, FGF signaling appeared not to be involved in human hypoblast formation [9,10].…”
Section: Introductionmentioning
confidence: 94%
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“…When human pre-implantation embryos were grown in the presence of ERK inhibitors to the blastocyst stage, there was no apparent effect on the formation of the PE (Kuijk et al, 2012;Roode et al, 2012;Van der Jeught et al, 2013), as would have been predicted from the mouse, suggesting that the formation of EPI versus PE is not under the tight control of FGF levels in the human. In addition, levels of FGF receptors are low in the human TE, which does not proliferate in response to FGF (Kunath et al, 2014).…”
Section: Blastocyst: Conservation and Divergence Of Lineage Functionsmentioning
confidence: 76%
“…M4287; Sigma). For standard hESC lines UGent11-5, UGent11-6, and UGent11-7, culturing from blastocyst to hESC stage was carried out in a low-oxygen environment at 37°C, consisting of 6% CO2, and 5% O2, using standard hESC medium [26,33]. Within approximately 7 days, hESCs outgrowths were cut mechanically, transferred to freshly inactivated MEFs, and continually mechanically passaged until several colonies appeared.…”
Section: Hesc Derivation and Culturementioning
confidence: 99%