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LIF-induced Stat3 signaling suppresses FGF1-induced Erk1/2 activation to inhibit the downstream differentiation in mouse embryonic stem cells.
MedLine Citation:
PMID:  23205673     Owner:  NLM     Status:  Publisher    
Abstract In regular culture conditions with leukemia inhibitory factor (LIF), the majority of mouse embryonic stem cells (mESCs) are maintained in a self-renewal stage; very few mESCs have differentiated morphology. When LIF is withdrawn, mESCs tend to differentiate; this differentiation process can be enhanced by the introduction of exogenous FGF. Here, we show that even in the presence of exogenous FGF1, mESCs can maintain self-renewal and expression of pluripotency markers in the presence of LIF. To elucidate the mechanism in which LIF dominates over FGF1, extracellular signal-regulated kinase 1/2 (Erk1/2) signaling of mESCs cultured in medium containing FGF1 or LIF/FGF1 was examined. The results demonstrate that Erk1/2 was activated by FGF1 in the absence of LIF; however, the FGF1-induced Erk1/2 phosphorylation was suppressed when LIF was introduced. Moreover, FGF1-Erk1/2 down-regulation was inhibited by signal transducer and activator of transcription 3 (Stat3) inhibitor WP1066, suggesting that LIF-induced Stat3 activation plays an important role in FGF1-Erk1/2 inhibition in mESCs. We further demonstrate that the binding affinity of phospho-Erk1/2 and Sprouty2 was increased via Stat3 activation. Binding of phospho-Erk1/2 and Sprouty2 blocks the activation of Erk1/2 signaling, thus inhibiting the downstream differentiation process in mESCs. Our findings demonstrate, for the first time, that LIF-induced Stat3 phosphorylation plays an important role in promoting the binding of phospho-Erk1/2 and Sprouty2, and thus inhibiting FGF-induced differentiation.
Jen-Wei Liu; Yi-Chao Hsu; Chien-Yu Kao; Hong-Lin Su; Ing-Ming Chiu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Stem cells and development     Volume:  -     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, , Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan;
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