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Blood, 15 September 2005, Vol. 106, No. 6, pp. 1948-1955. Prepublished online as a Blood First Edition Paper on May 31, 2005; DOI 10.1182/blood-2004-12-4872. This Article Full Text (PDF) All Versions of this Article: 2004-12-4872v1 106/6/1948    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 Hirai, H. Articles by Nishikawa, S.-I. Search for Related Content PubMed PubMed Citation Articles by Hirai, H. Articles by Nishikawa, S.-I. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 22, 2004 Accepted May 16, 2005 Involvement of Runx1 in the downregulation of fetal liver kinase-1 (Flk-1) expression during transition of endothelial cells to hematopoietic cells Hideyo Hirai*, Igor M Samokhvalov, Tetsuhiro Fujimoto, Satomi Nishikawa, Jiro Imanishi, and Shin-Ichi Nishikawa Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan RIKEN Center for Developmental Biology, Kobe, Japan European Molecular Biology Laboratory, Monterotondo, Italy * Corresponding author; email: hhirai{at}koto.kpu-m.ac.jp. During early mouse embryogenesis, fetal liver kinase (Flk)-1, a receptor for vascular endothelial growth factor, and Runx1, a runt domain transcription factor, have prerequisite roles in the generation of hematopoietic lineages. Flk-1 expression is maintained in successive stages from mesoderm to endothelial cells and is downregulated in nascent hematopoietic cells, whereas Runx1 is expressed in embryonic sites of hematopoietic cells de novo generation as well as in practically all hematopoietic organs. Here we show that Runx1 represses Flk-1 during the development of hemogenic endothelial cells into hematopoietic cells. We established embryonic stem cell clones carrying the Venus gene, a modified version of yellow fluorescent protein, in the Runx1 locus and cultured them on OP9 cells without leukemia inhibitory factor. Flk-1+ cells appeared on day 3.5 and Runx1+ cells first appeared from the Flk-1+ fraction at day 4.5. The Flk-1+Runx1+ cells rapidly stopped expressing Flk-1 with further incubation, and eventually gave rise to CD45+ or TER119+ cells. Runx1 repressed the Flk-1 promoter transcriptional activity in an endothelial cell line and this repression required intact DNA-binding and transactivating domains of Runx1 protein. The repressor activity of Runx1 on endogenous Flk-1 was also confirmed by overexpressing Runx1 in embryonic stem cell differentiation cultures. These results provide novel insight into the role of Runx1 during the development of hematopoietic cell lineages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. E. Broxmeyer, S. Sehra, S. Cooper, L. M. Toney, S. Kusam, J. J. Aloor, C. C. Marchal, M. C. Dinauer, and A. L. Dent Aberrant Regulation of Hematopoiesis by T Cells in BAZF-Deficient Mice Mol. Cell. Biol., August 1, 2007; 27(15): 5275 - 5285. [Abstract] [Full Text] [PDF] F. Timmermans, F. Van Hauwermeiren, M. De Smedt, R. Raedt, F. Plasschaert, M. L. De Buyzere, T. C. Gillebert, J. Plum, and B. Vandekerckhove Endothelial Outgrowth Cells Are Not Derived From CD133+ Cells or CD45+ Hematopoietic Precursors Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1572 - 1579. [Abstract] [Full Text] [PDF] M. Abe and Y. Sato Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies. Genes Cells, July 1, 2006; 11(7): 719 - 729. [Abstract] [Full Text] [PDF]

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