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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

(2013) STEM CELLS AND DEVELOPMENT. 22(2). p.296-306
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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 GSK3 beta 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 GSK3 beta pathway on embryo preimplantation development, early lineage segregation, and subsequent embryonic stem cell derivation in the humans. We did not observe any effect on blastocyst formation, but small-molecule inhibition did affect the number of OCT3/4- and NANOG-positive cells in the human ICM. We found that combined inhibition of the FGF/MEK/Erk and GSK3 beta pathways by PD0325901 and CHIR99021, respectively, resulted in ICMs containing significantly more OCT3/4-positive cells. Inhibition of FGF/MEK/Erk alone as well as in combination with inhibition of GSK3 beta significantly increased the number of NANOG-positive cells in blastocysts possessing good-quality ICMs. Secondly, we verified the influence of this increased pluripotency after 2i culture on the efficiency of stem cell derivation. Similar human embryonic stem cell (hESC) derivation rates were observed after 2i compared to control conditions, resulting in 2 control hESC lines and 1 hESC line from an embryo cultured in 2i conditions. In conclusion, we demonstrated that FGF/MEK/Erk and GSK3 beta signaling increases the number of OCT3/4- and NANOG-positive cells in the human ICM, but does not improve stem cell derivation.
Keywords
DIFFERENTIATION, RAT BLASTOCYSTS, PREIMPLANTATION EMBRYOS, MOUSE BLASTOCYST, PRIMITIVE ENDODERM, GENERATION, EXPRESSION, SEGREGATION, TROPHECTODERM, LINES

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MLA
Van der Jeught, Margot, et al. “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.” STEM CELLS AND DEVELOPMENT, vol. 22, no. 2, 2013, pp. 296–306, doi:10.1089/scd.2012.0256.
APA
Van der Jeught, M., O’Leary, T., Ghimire, S., Lierman, S., Duggal, G., Versieren, K., … De Sutter, P. (2013). 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. STEM CELLS AND DEVELOPMENT, 22(2), 296–306. https://doi.org/10.1089/scd.2012.0256
Chicago author-date
Van der Jeught, Margot, Thomas O’Leary, Sabitri Ghimire, Sylvie Lierman, Galbha Duggal, Karen Versieren, Dieter Deforce, Susana Chuva de Sousa Lopes, Björn Heindryckx, and Petra De Sutter. 2013. “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.” STEM CELLS AND DEVELOPMENT 22 (2): 296–306. https://doi.org/10.1089/scd.2012.0256.
Chicago author-date (all authors)
Van der Jeught, Margot, Thomas O’Leary, Sabitri Ghimire, Sylvie Lierman, Galbha Duggal, Karen Versieren, Dieter Deforce, Susana Chuva de Sousa Lopes, Björn Heindryckx, and Petra De Sutter. 2013. “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.” STEM CELLS AND DEVELOPMENT 22 (2): 296–306. doi:10.1089/scd.2012.0256.
Vancouver
1.
Van der Jeught M, O’Leary T, Ghimire S, Lierman S, Duggal G, Versieren K, et al. 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. STEM CELLS AND DEVELOPMENT. 2013;22(2):296–306.
IEEE
[1]
M. Van der Jeught et al., “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,” STEM CELLS AND DEVELOPMENT, vol. 22, no. 2, pp. 296–306, 2013.
@article{3144751,
  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 GSK3 beta 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 GSK3 beta pathway on embryo preimplantation development, early lineage segregation, and subsequent embryonic stem cell derivation in the humans. We did not observe any effect on blastocyst formation, but small-molecule inhibition did affect the number of OCT3/4- and NANOG-positive cells in the human ICM. We found that combined inhibition of the FGF/MEK/Erk and GSK3 beta pathways by PD0325901 and CHIR99021, respectively, resulted in ICMs containing significantly more OCT3/4-positive cells. Inhibition of FGF/MEK/Erk alone as well as in combination with inhibition of GSK3 beta significantly increased the number of NANOG-positive cells in blastocysts possessing good-quality ICMs. Secondly, we verified the influence of this increased pluripotency after 2i culture on the efficiency of stem cell derivation. Similar human embryonic stem cell (hESC) derivation rates were observed after 2i compared to control conditions, resulting in 2 control hESC lines and 1 hESC line from an embryo cultured in 2i conditions. In conclusion, we demonstrated that FGF/MEK/Erk and GSK3 beta signaling increases the number of OCT3/4- and NANOG-positive cells in the human ICM, but does not improve stem cell derivation.}},
  author       = {{Van der Jeught, Margot and O'Leary, Thomas and Ghimire, Sabitri and Lierman, Sylvie and Duggal, Galbha and Versieren, Karen and Deforce, Dieter and Lopes, Susana Chuva de Sousa and Heindryckx, Björn and De Sutter, Petra}},
  issn         = {{1547-3287}},
  journal      = {{STEM CELLS AND DEVELOPMENT}},
  keywords     = {{DIFFERENTIATION,RAT BLASTOCYSTS,PREIMPLANTATION EMBRYOS,MOUSE BLASTOCYST,PRIMITIVE ENDODERM,GENERATION,EXPRESSION,SEGREGATION,TROPHECTODERM,LINES}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{296--306}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1089/scd.2012.0256}},
  volume       = {{22}},
  year         = {{2013}},
}

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