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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1357-1365. Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-05-1916. This Article Full Text (PDF) All Versions of this Article: 2005-05-1916v1 107/4/1357    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 Matsumoto, N. Articles by Friedman, S. L Search for Related Content PubMed PubMed Citation Articles by Matsumoto, N. Articles by Friedman, S. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 11, 2005 Accepted September 30, 2005 Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6 Nobuyuki Matsumoto, Atsushi Kubo, Huixian Liu, Kuniharu Akita, Friedrich Laub, Francesco Ramirez, Gordon Keller, and Scott L Friedman* Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, Department Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, Department Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY, USA; CEINGE-Biotecnologie Avanzate, Naples, Italy * Corresponding author; email: Scott.Friedman{at}mssm.edu. Kruppel like factor 6 (KLF6) is a member of a growing family of transcription factors that share a common three C2H2 zinc finger DNA binding domain and have broad activity in regulating proliferation and development. We have previously established that Klf6 is expressed in neuronal tissue, hindgut, heart, lung, kidney and limb buds during mid-gestation. To explore the potential role of Klf6 in mouse development, we analyzed Klf6-/- mice and found that the homozygous mutation is embryonic lethal by E 12.5 and associated with markedly reduced hematopoiesis and poorly organized yolk sac vascularization. Additionally, mRNA levels of Scl and Gata1 were reduced by ~80% in Klf6-/- yolk sacs. To further analyze this phenotype, we generated Klf6-/- embryonic stem (ES) cells by homologous recombination, and compared their capacity to differentiate into the hematopoietic lineage to that of either Klf6+/- or Klf6+/+ ES cells. Consistent with the phenotype in the early embryo, Klf6-/- ES cell displayed significant hematopoietic defects following differentiation into EBs. Prolongation of epiblast-like cells and delays in mesoderm induction were also observed in the Klf6-/- EBs, associated with delayed expression of Brachyury, Klf1 and Gata1. Forced expression of KLF6 using a tet-inducible system enhanced the hematopoietic potential of wild type EBs. Collectively these findings implicate Klf6 in ES cell differentiation and hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. C. Leow, B.-e. Wang, J. Ross, S. M. Chan, J. Zha, R. A. D. Carano, G. Frantz, M. M. Shen, F. J. de Sauvage, and W.-Q. Gao Prostate-specific Klf6 Inactivation Impairs Anterior Prostate Branching Morphogenesis through Increased Activation of the Shh Pathway J. Biol. Chem., July 31, 2009; 284(31): 21057 - 21065. [Abstract] [Full Text] [PDF] S. M. 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Immunol., April 15, 2008; 180(8): 5645 - 5652. [Abstract] [Full Text] [PDF] I. Bentov, G. Narla, H. Schayek, K. Akita, S. R. Plymate, D. LeRoith, S. L. Friedman, and H. Werner Insulin-Like Growth Factor-I Regulates Kruppel-Like Factor-6 Gene Expression in a p53-Dependent Manner Endocrinology, April 1, 2008; 149(4): 1890 - 1897. [Abstract] [Full Text] [PDF] P. Basu, T. K. Lung, W. Lemsaddek, T. G. Sargent, D. C. Williams Jr, M. Basu, L. C. Redmond, J. B Lingrel, J. L. Haar, and J. A. Lloyd EKLF and KLF2 have compensatory roles in embryonic {beta}-globin gene expression and primitive erythropoiesis Blood, November 1, 2007; 110(9): 3417 - 3425. [Abstract] [Full Text] [PDF] M. Kobayashi and M. Yamamoto Regulation of GATA1 Gene Expression J. Biochem., July 1, 2007; 142(1): 1 - 10. [Abstract] [Full Text] [PDF] A. P. W. Funnell, C. A. Maloney, L. J. Thompson, J. Keys, M. Tallack, A. C. Perkins, and M. 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