All three authors are equal contributors.
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 16 JUL 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 9, pages 1476–1486, September 2010
How to Cite
Cha, Y., Moon, B.-h., Lee, M.-o., Ahn, H.-j., Lee, H.-j., Lee, K.-a., Fornace, A. J., Kim, K.-s., Cha, H.-j. and Park, K.-s. (2010), Zap70 Functions to Maintain Stemness of Mouse Embryonic Stem Cells by Negatively Regulating Jak1/Stat3/c-Myc Signaling. STEM CELLS, 28: 1476–1486. doi: 10.1002/stem.470
Author contributions: Y.C., B.-H.M., M.-O.L.: major contributor for collection and assembly of data; H.J.A., H.-J.L.: collection and assembly of data; K.-A.L., A.J.F.: conception and design, data analysis and interpretation; K.-S.K., H.-J.C., K.-S.P.: conception and design, manuscript writing, data analysis and interpretation. Y.C., B.-H.M., M.-O.L., H.-J.C., and K.-S.P. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS 16 July, 2010.
- Issue online: 16 JUL 2010
- Version of Record online: 16 JUL 2010
- Manuscript Accepted: 17 JUN 2010
- Manuscript Received: 25 JAN 2010
- National Research Foundation of Korea (NRF) funded by the Korea Goverment. Grant Number: KRF-2008-313-C00703
- Korea Science and Engineering Foundation
- Korean government (MOST). Grant Numbers: 20090084075, 313-2008-2-C00703
- National Institute of Health. Grant Number: MH087903
- Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea. Grant Number: (SC-5130)
- Mouse embryonic stem cells;
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 self-renewal 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; 28:1476–1486.