Journal
STEM CELLS
Volume 28, Issue 9, Pages 1476-1486Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.470
Keywords
Zap70; Mouse embryonic stem cells; Jak/ Stat3; c-Myc; SHP-1; LIFR; Self-renewal; Pluripotency; Stemness
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Funding
- Korea Goverment [KRF-2008-313-C00703]
- Korea Science and Engineering Foundation (KOSEF) of the Korean government (MOST) [20090084075, 313-2008-2-C00703]
- National Institute of Health [MH087903]
- Stem Cell Research Center [SC5130]
- Ministry of Science and Technology, Republic of Korea
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Zeta-chain-associated protein kinase-70 (Zap70), a Syk family tyrosine kinase, has been reported to be present exclusively in normal T-cells, natural killer cells, and B cells, serving as a pivotal regulator of antigen-mediated receptor signaling and development. In this study, we report that Zap70 is expressed in undifferentiated mouse embryonic stem cells (mESCs) and may critically regulate selfrenewal and pluripotency in mESCs. We found that Zap70 knocked-down mESCs (Zap70KD) show sustained self-renewal and defective differentiation. In addition, we present evidence that the sustained self-renewal in Zap70KD is associated with enhanced Jak/Stat3 signaling and c-Myc induction. These altered signaling appears to result from upregulated leukemia inhibitory factor receptor and downregulated src homology region 2 domain containing phosphatase 1 (SHP-1) phosphatase activity. On the basis of these results, we propose that in undifferentiated mESCs, Zap70 plays important roles in modulating the balance between self-renewal capacity and pluripotent differentiation ability as a key regulator of the Jak/Stat3/ c-Myc signaling pathway. STEM CELLS 2010; 127: 1476-1486
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