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• W2096096048 abstract "Reprogramming of a differentiated cell back to a naive pluripotent identity is thought to occur by several independent mechanisms. Two such mechanisms include NANOG and activated STAT3 (pSTAT3), known master regulators of naive pluripotency acquisition [1-5]. Here, we investigated the relationship between NANOG and pSTAT3 during the establishment and maintenance of naive pluripotency. Surprisingly, we found that NANOG enhances LIF signal transduction, resulting in elevated pSTAT3. This is mediated, at least in part, by suppression of the expression of the LIF/STAT3 negative regulator SOCS3. We also discovered NANOG to be limiting for the expression of KLF4, a canonical Yamanaka reprogramming factor [6] and key pSTAT3 target [2, 7, 8]. KLF4 expression resulted from the codependent and synergistic action of NANOG and pSTAT3 in embryonic stem cells and during initiation of reprogramming. Additionally, within 48 hr, the combined actions of NANOG and pSTAT3 in a reprogramming context resulted in reactivation of genes associated with naive pluripotency. Importantly, we show that NANOG can be bypassed during reprogramming by exogenous provision of its downstream effectors, namely pSTAT3 elevation and KLF4 expression. In conclusion, we propose that mechanisms of reprogramming are linked, rather than independent, and are centered on a small number of genes, including NANOG." @default.
• W2096096048 created "2016-06-24" @default.
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• W2096096048 date "2014-02-01" @default.
• W2096096048 modified "2023-10-05" @default.
• W2096096048 title "NANOG Amplifies STAT3 Activation and They Synergistically Induce the Naive Pluripotent Program" @default.
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• W2096096048 doi "https://doi.org/10.1016/j.cub.2013.12.040" @default.
• W2096096048 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3982126" @default.
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