Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/62942
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dc.contributor.authorYeo, Jia Chien
dc.date.accessioned2015-05-04T04:12:53Zen
dc.date.available2015-05-04T04:12:53Zen
dc.date.copyright2015en
dc.date.issued2015en
dc.identifier.citationYeo, J. C. (2015). The role of Mek/Erk signalling inhibition and Krüppel-like factor 2 in mouse ground state pluripotency. Doctoral thesis, Nanyang Technological University, Singapore.en
dc.identifier.urihttps://hdl.handle.net/10356/62942en
dc.description.abstractThe maintenance of undifferentiated mouse embryonic stem cells (mESCs) requires the presence of LIF and serum. Interestingly, by using two chemical molecules to inhibit both the pro-differentiative Fgf/Mek/Erk and Gsk3/Tcf3 pathways in mESCs (dual inhibition or “2i”), a pluripotent “ground state”, resembling the mouse pre-implantation epiblast can be established without the need for LIF and serum. While Gsk3-inhibition is known to alleviate Tcf3-mediated repression of Esrrb, the molecular mechanism downstream of Mek/Erk inhibition remains to be identified. Here, it was uncovered that Erk2 phosphorylates the Krüppel-like factor 2 (Klf2), leading to Klf2 proteasomal degradation. Mek/Erk inhibition during 2i conditions thus serves to halt Klf2 phospho-degradation, leading to Klf2 protein stabilisation and maintenance of ground state pluripotency. Indeed, while Klf2-null mESCs are viable under LIF/Serum, they undergo apoptosis during 2i culture. Additionally, it was found that Klf2 overexpression is sufficient to replace Mek-inhibition, allowing for mESC self-renewal under Gsk3-inhibition alone. Taken together, this study highlights the importance of Klf2 during 2i conditions, and defines the Mek/Erk/Klf2 pathway with the Gsk3/Tcf3/Esrrb axis to establish ground state pluripotency.en
dc.format.extent221 p.en
dc.language.isoenen
dc.subjectDRNTU::Science::Biological sciences::Molecular biologyen
dc.titleThe role of Mek/Erk signalling inhibition and Krüppel-like factor 2 in mouse ground state pluripotencyen
dc.typeThesisen
dc.contributor.supervisorNg Huck Huien
dc.contributor.supervisorSu I-Hsinen
dc.contributor.schoolSchool of Biological Sciencesen
dc.description.degreeDOCTOR OF PHILOSOPHY (SBS)en
dc.contributor.organizationA*STAR Genome Institute of Singaporeen
dc.identifier.doi10.32657/10356/62942en
item.grantfulltextopen-
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