Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/82151
Title: Klf2 Is an Essential Factor that Sustains Ground State Pluripotency
Authors: Yeo, Jia-Chi
Jiang, Jianming
Tan, Zi-Ying
Yim, Guo-Rong
Ng, Jia-Hui
Göke, Jonathan
Kraus, Petra
Liang, Hongqing
Gonzales, Kevin Andrew Uy
Chong, Han-Chung
Tan, Cheng-Peow
Lim, Yee-Siang
Tan, Nguan-Soon
Lufkin, Thomas
Ng, Huck-Hui
Issue Date: 2014
Source: Yeo, J.-C., Jiang, J., Tan, Z.-Y., Yim, G.-R., Ng, J.-H., Göke, J., et al. (2014). Klf2 Is an Essential Factor that Sustains Ground State Pluripotency. Cell Stem Cell, 14(6), 864-872.
Series/Report no.: Cell Stem Cell
Abstract: The maintenance of mouse embryonic stem cells (mESCs) requires LIF and serum. However, a pluripotent “ground state,” bearing resemblance to preimplantation mouse epiblasts, can be established through dual inhibition (2i) of both prodifferentiation Mek/Erk and Gsk3/Tcf3 pathways. While Gsk3 inhibition has been attributed to the transcriptional derepression of Esrrb, the molecular mechanism mediated by Mek inhibition remains unclear. In this study, we show that Krüppel-like factor 2 (Klf2) is phosphorylated by Erk2 and that phospho-Klf2 is proteosomally degraded. Mek inhibition hence prevents Klf2 protein phosphodegradation to sustain pluripotency. Indeed, while Klf2-null mESCs can survive under LIF/Serum, they are not viable under 2i, demonstrating that Klf2 is essential for ground state pluripotency. Importantly, we also show that ectopic Klf2 expression can replace Mek inhibition in mESCs, allowing the culture of Klf2-null mESCs under Gsk3 inhibition alone. Collectively, our study defines the Mek/Erk/Klf2 axis that cooperates with the Gsk3/Tcf3/Esrrb pathway in mediating ground state pluripotency.
URI: https://hdl.handle.net/10356/82151
http://hdl.handle.net/10220/41099
ISSN: 1934-5909
DOI: 10.1016/j.stem.2014.04.015
Rights: © 2014 Elsevier Inc.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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