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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-03-0740. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0740v1 101/1/134    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 Buitenhuis, M. Articles by Koenderman, L. Search for Related Content PubMed PubMed Citation Articles by Buitenhuis, M. Articles by Koenderman, L. Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 134-142 HEMATOPOIESIS Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells Miranda Buitenhuis, Belinda Baltus, Jan-Willem J. Lammers, Paul J. Coffer, and Leo Koenderman From the Department of Pulmonary Diseases, University Medical Center, Utrecht, The Netherlands. Signal transducers and activators of transcription (STATs) have been reported to play a critical role in the differentiation of several myeloid cell lines, although the importance of STATs in the differentiation of primary human hematopoietic cells remains to be established. Terminal eosinophil differentiation is induced by interleukin-5 (IL-5), which has also been demonstrated to activate STAT5. We have investigated whether STAT5 plays a critical role during eosinophil differentiation using umbilical cord blood-derived CD34+ cells. In this ex vivo system, STAT5 expression and activation are high early during differentiation, and STAT5 protein expression is down-regulated during the final stages of eosinophil differentiation. Retroviral transductions were performed to ectopically express wild-type and dominant-negative STAT5a (STAT5a750) in CD34+ cells. Transduction of cells with STAT5a resulted in enhanced proliferation compared with cells transduced with empty vector alone. Interestingly, ectopic expression of STAT5a also resulted in accelerated differentiation. In contrast, ectopic expression of STAT5a750 resulted in a block in differentiation, whereas proliferation was also severely inhibited. Similar results were obtained with dominant-negative STAT5b. Forced expression of STAT5a enhanced expression of the STAT5 target genes Bcl-2 and p21WAF/Cip1, suggesting they may be important in STAT5a-mediated eosinophil differentiation. These results demonstrate that STAT5 plays a critical role in eosinophil differentiation of primary human hematopoietic cells. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. H. Ulfman, V. M. Kamp, C. W. van Aalst, L. P. Verhagen, M. E. Sanders, K. A. Reedquist, M. Buitenhuis, and L. Koenderman Homeostatic Intracellular-Free Ca2+ Is Permissive for Rap1-Mediated Constitutive Activation of {alpha}4 Integrins on Eosinophils J. Immunol., April 15, 2008; 180(8): 5512 - 5519. [Abstract] [Full Text] [PDF] M. Buitenhuis, L. P. Verhagen, H. W. M. van Deutekom, A. Castor, S. Verploegen, L. Koenderman, S.-E. W. Jacobsen, and P. J. Coffer Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis Blood, January 1, 2008; 111(1): 112 - 121. [Abstract] [Full Text] [PDF] M. Buitenhuis, L. P. Verhagen, J. Cools, and P. J. Coffer Molecular Mechanisms Underlying FIP1L1-PDGFRA-Mediated Myeloproliferation Cancer Res., April 15, 2007; 67(8): 3759 - 3766. [Abstract] [Full Text] [PDF] M. Rosas, P. F. Dijkers, C. L. Lindemans, J.-W. J. Lammers, L. Koenderman, and P. J. Coffer IL-5-mediated eosinophil survival requires inhibition of GSK-3 and correlates with {beta}-catenin relocalization J. Leukoc. Biol., July 1, 2006; 80(1): 186 - 195. [Abstract] [Full Text] [PDF] M. A. Meyn III, S. J. Schreiner, T. P. Dumitrescu, G. J. Nau, and T. E. Smithgall Src Family Kinase Activity Is Required for Murine Embryonic Stem Cell Growth and Differentiation Mol. Pharmacol., November 1, 2005; 68(5): 1320 - 1330. [Abstract] [Full Text] [PDF] J. J. Schuringa, K. Y. Chung, G. Morrone, and M. A.S. Moore Constitutive Activation of STAT5A Promotes Human Hematopoietic Stem Cell Self-Renewal and Erythroid Differentiation J. Exp. Med., September 7, 2004; 200(5): 623 - 635. [Abstract] [Full Text] [PDF] H. H. Versteeg, C. A. Spek, S. H. Slofstra, S. H. Diks, D. J. Richel, and M. P. Peppelenbosch FVIIa:TF Induces Cell Survival via G12/G13-Dependent Jak/STAT Activation and BclXL Production Circ. Res., April 30, 2004; 94(8): 1032 - 1040. [Abstract] [Full Text] [PDF]

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