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Blood, 15 January 2005, Vol. 105, No. 2, pp. 635-637. Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-07-2681. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2004-07-2681v1 105/2/635    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Chan, R. J Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Chan, R. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 15, 2004 Accepted August 30, 2004 Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4 Yanjun Li, Jeanette McClintick, Li Zhong, Howard J Edenberg, Mervin C Yoder, and Rebecca J Chan* Departments of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, USA Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, USA Departments of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Departments of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA * Corresponding author; email: rchan{at}iupui.edu. Embryonic stem (ES) cells homozygous for a Shp-2 mutation (Shp-246-110) demonstrate leukemia inhibitory factor (LIF) hypersensitivity and increased LIF-stimulated STAT3 phosphorylation. We hypothesized that LIF-responsive genes in Shp-246-110 cells would represent potential candidates for molecules vital for ES cell self-renewal. Using microarray analysis, we detected 41 genes whose expression was modified by LIF in Shp-246-110 ES cells. Induction of two significantly up-regulated genes, SOCS-3 and Kruppel-like factor 4 (Klf4), was verified using Northern blotting. ES cells over-expressing SOCS-3 had an increased capacity to differentiate to hematopoietic progenitors, rather than to self-renew. In contrast, ES cells over-expressing Klf4 had a greater capacity to self-renew based on secondary embryoid body (EB) formation. Klf4-transduced d6 EBs expressed higher levels of Oct-4, consistent with the notion that Klf4 promotes ES cell self-renewal. These findings verify the negative role of SOCS-3 on LIF signaling and provide a novel role for Klf4 in ES cell function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Savarese, A. Davila, R. Nechanitzky, I. De La Rosa-Velazquez, C. F. Pereira, R. Engelke, K. Takahashi, T. Jenuwein, T. Kohwi-Shigematsu, A. G. Fisher, et al. Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression Genes & Dev., November 15, 2009; 23(22): 2625 - 2638. [Abstract] [Full Text] [PDF] M. Godmann, I. Gashaw, K. Eildermann, S. Schweyer, M. Bergmann, R.I. Skotheim, and R. Behr The pluripotency transcription factor Kruppel-like factor 4 is strongly expressed in intratubular germ cell neoplasia unclassified and seminoma Mol. Hum. Reprod., August 1, 2009; 15(8): 479 - 488. [Abstract] [Full Text] [PDF] G. Guo, J. Yang, J. Nichols, J. S. Hall, I. Eyres, W. Mansfield, and A. 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[Abstract] [Full Text] [PDF] S. Yamanaka Pluripotency and nuclear reprogramming Phil Trans R Soc B, June 27, 2008; 363(1500): 2079 - 2087. [Abstract] [Full Text] [PDF] T. Kondo, P. L. Sheets, D. A. Zopf, H. L. Aloor, T. R. Cummins, R. J. Chan, and E. Hashino Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells PNAS, April 15, 2008; 105(15): 5780 - 5785. [Abstract] [Full Text] [PDF] R. Behr, C. Deller, M. Godmann, T. Muller, M. Bergmann, R. Ivell, and K. Steger Kruppel-like factor 4 expression in normal and pathological human testes Mol. Hum. Reprod., November 1, 2007; 13(11): 815 - 820. [Abstract] [Full Text] [PDF] A. Hamik, Z. Lin, A. Kumar, M. Balcells, S. Sinha, J. Katz, M. W. Feinberg, R. E. Gerszten, E. R. Edelman, and M. K. Jain Kruppel-like Factor 4 Regulates Endothelial Inflammation J. Biol. Chem., May 4, 2007; 282(18): 13769 - 13779. [Abstract] [Full Text] [PDF] H. 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