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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Brief report 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 From the Departments of Pediatrics, Medical and Molecular Genetics, Biochemistry and Molecular Biology, and Microbiology and Immunology, Herman B Wells Center for Pediatric Research, and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN. Embryonic stem (ES) cells homozygous for a Shp-2 mutation (Shp-246-110) demonstrate leukemia inhibitory factor (LIF) hypersensitivity and increased LIF-stimulated phosphorylation of signal transducer and activator of transcription (STAT3). 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 2 significantly up-regulated genes, suppressor of cytokine signaling–3 (SOCS-3) and Krüppel-like factor 4 (Klf4), was verified using Northern blotting. ES cells overexpressing SOCS-3 had an increased capacity to differentiate to hematopoietic progenitors, rather than to self-renew. In contrast, ES cells overexpressing 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. 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[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. Niwa How is pluripotency determined and maintained? Development, February 15, 2007; 134(4): 635 - 646. [Abstract] [Full Text] [PDF] O. M. Pello, M. del Carmen Moreno-Ortiz, J. M. Rodriguez-Frade, L. Martinez-Munoz, D. Lucas, L. Gomez, P. Lucas, E. Samper, M. Aracil, C. Martinez-A, et al. SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade Blood, December 1, 2006; 108(12): 3928 - 3937. [Abstract] [Full Text] [PDF] Y. Nakatake, N. Fukui, Y. Iwamatsu, S. Masui, K. Takahashi, R. Yagi, K. Yagi, J.-i. Miyazaki, R. Matoba, M. S. H. Ko, et al. Klf4 Cooperates with Oct3/4 and Sox2 To Activate the Lefty1 Core Promoter in Embryonic Stem Cells Mol. Cell. Biol., October 15, 2006; 26(20): 7772 - 7782. [Abstract] [Full Text] [PDF]

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