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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2372-2379. Prepublished online as a Blood First Edition Paper on November 23, 2004; DOI 10.1182/blood-2004-07-2547. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-07-2547v1 105/6/2372    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 Suzuki, H. Articles by Miyazono, K. Search for Related Content PubMed PubMed Citation Articles by Suzuki, H. Articles by Miyazono, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 7, 2004 Accepted November 8, 2004 Roles of vascular endothelial growth factor receptor 3 signaling in differentiation of mouse embryonic stem cell-derived vascular progenitor cells into endothelial cells Hiroyuki Suzuki, Tetsuro Watabe, Mitsuyasu Kato, Keiji Miyazawa, and Kohei Miyazono* Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Biochemistry, Cancer Institute of Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan Department of Experimental Pathology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaragi, Japan * Corresponding author; email: miyazono-ind{at}umin.ac.jp. Vascular endothelial growth factor receptor 2 (VEGFR2/Flk1)-positive cells derived from embryonic stem (ES) cells serve as vascular progenitors, which differentiate into endothelial cells (ECs) in the presence of VEGF-A. VEGFR3/Flt4 signaling is known to be important for the development of lymphatic endothelial cells (LECs). To elucidate the roles of VEGFR3 signaling in the differentiation of vascular progenitor cells into ECs, we introduced various types of VEGFR3 cDNAs into mouse ES cells. VEGF-C, a ligand for VEGFR2 and VEGFR3, stimulated the endothelial differentiation of the VEGFR2+ cells transfected with the VEGFR3 cDNA, but not those transfected with kinase-negative mutants of VEGFR3. The VEGFR3-transfected ECs exhibited high expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), one of the markers of LECs, and showed efficient binding of hyaluronan. VEGF-C(C152S), which is able to activate VEGFR3 but not VEGFR2, failed to induce the endothelial differentiation of mock- and VEGFR3-transfected VEGFR2+ cells, suggesting the essential role of VEGFR2 signaling for endothelial differentiation. Furthermore, kinase-negative mutants of VEGFR3 prevented the VEGF-C-mediated endothelial differentiation of the vascular progenitor cells. Thus, VEGFR2 signaling is required for the endothelial differentiation of mouse ES cells induced by VEGF-C, and VEGFR3 signaling may confer lymphatic endothelial-like phenotypes to ECs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Sase, T. Watabe, K. Kawasaki, K. Miyazono, and K. Miyazawa VEGFR2-PLC{gamma}1 axis is essential for endothelial specification of VEGFR2+ vascular progenitor cells J. Cell Sci., September 15, 2009; 122(18): 3303 - 3311. [Abstract] [Full Text] [PDF] C. Conrad, H. Niess, R. Huss, S. Huber, I. von Luettichau, P. J. Nelson, H. C. Ott, K.-W. Jauch, and C. J. Bruns Multipotent Mesenchymal Stem Cells Acquire a Lymphendothelial Phenotype and Enhance Lymphatic Regeneration In Vivo Circulation, January 20, 2009; 119(2): 281 - 289. [Abstract] [Full Text] [PDF] M. Oka, C. Iwata, H. I. Suzuki, K. Kiyono, Y. Morishita, T. Watabe, A. Komuro, M. R. Kano, and K. Miyazono Inhibition of endogenous TGF-{beta} signaling enhances lymphangiogenesis Blood, May 1, 2008; 111(9): 4571 - 4579. [Abstract] [Full Text] [PDF] K. Kawasaki, T. Watabe, H. Sase, M. Hirashima, H. Koide, Y. Morishita, K. Yuki, T. Sasaoka, T. Suda, M. Katsuki, et al. Ras signaling directs endothelial specification of VEGFR2+ vascular progenitor cells J. Cell Biol., April 3, 2008; 181(1): 131 - 141. [Abstract] [Full Text] [PDF]

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