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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 (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 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. Social Bookmarking                   What's this? Submitted March 11, 2002 Accepted August 5, 2002 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* Department of Pulmonary Diseases, University Medical Center, Utrecht, The Netherlands * Corresponding author; email: L.Koenderman{at}hli.azu.nl. Signal Transducers and Activators of Transcription (STATs) have been reported to play a critical role in differentiation of several myeloid cell lines, although the importance of STATs in differentiation of primary human hematopoietic cells remains to be established. Terminal eosinophil differentiation is induced by 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 (UCB) derived CD34+ cells. In this ex-vivo system, both 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 both wild-type and dominant-negative STAT5a (STAT5a750) in CD34+ cells. Transduction of cells with STAT5a resulted in enhanced proliferation compared to cells transduced with empty vector alone. Interestingly, ectopic expression of STAT5a also resulted in an accelerated differentiation. In contrast, ectopic expression of STAT5a750 resulted in a block in differentiation while 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Beekman, L. P. Verhagen, N. Geijsen, and P. J. Coffer Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor output Blood, October 29, 2009; 114(18): 3917 - 3927. [Abstract] [Full Text] [PDF] C. R. Geest, M. Buitenhuis, E. Vellenga, and P. J. Coffer Ectopic expression of C/EBP{alpha} and ID1 is sufficient to restore defective neutrophil development in low-risk myelodysplasia Haematologica, August 1, 2009; 94(8): 1075 - 1084. [Abstract] [Full Text] [PDF] R. Bedi, J. Du, A. K. Sharma, I. Gomes, and S. J. Ackerman Human C/EBP-{epsilon} activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation Blood, January 8, 2009; 113(2): 317 - 327. 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