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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-03-0944. This Article Full Text (PDF) All Versions of this Article: 2003-03-0944v1 102/9/3172    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 Kirito, K. Articles by Kaushansky, K. Search for Related Content PubMed PubMed Citation Articles by Kirito, K. Articles by Kaushansky, K. Social Bookmarking                   What's this? Submitted March 26, 2003 Accepted June 28, 2003 Thrombopoietin stimulates HoxB4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cells Keita Kirito, Norma Fox, and Kenneth Kaushansky* Department of Medicine, Division of Hematology/Oncology, University of California, San Diego, CA, USA * Corresponding author; email: kkaushansky{at}ucsd.edu. Thrombopoietin (TPO), the primary regulator of platelet production, also plays an important role in hematopoietic stem cell (HSC) biology. In previous studies we demonstrated that the self-renewal and expansion of HSCs is 10 to 20 times less robust in tpo-/- mice than in controls. In order to explore the molecular basis of this effect we postulated that HoxB4 might mediate at least part of the TPO effect on these cells. We first analyzed the effects of TPO on HoxB4 expression in primitive hematopoietic cell lines; TPO increased expression of the gene 2-3 fold in EML and UT-7/TPO cells. We also compared HoxB4 levels in a candidate HSC population derived from tpo-/- and control mice; HoxB4 expression was two to five fold lower in null HSCs. Of the numerous signal transduction molecules induced by TPO we found that p38 MAPK was responsible for the TPO-induced HOXB4 elevation. We also demonstrated that USF-1, a transcription factor previously shown to regulate HOXB4 expression, is also induced by TPO in a p38 dependent manner. Together these data provide a molecular pathway by which a growth factor can modulate a transcription factor and thereby help direct a critical developmental process. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. J. Lawrence, J. Christensen, S. Fong, Y.-L. Hu, I. Weissman, G. Sauvageau, R. K. Humphries, and C. Largman Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells Blood, December 1, 2005; 106(12): 3988 - 3994. [Abstract] [Full Text] [PDF] E. Verhoeyen, M. Wiznerowicz, D. Olivier, B. Izac, D. Trono, A. Dubart-Kupperschmitt, and F.-L. Cosset Novel lentiviral vectors displaying "early-acting cytokines" selectively promote survival and transduction of NOD/SCID repopulating human hematopoietic stem cells Blood, November 15, 2005; 106(10): 3386 - 3395. [Abstract] [Full Text] [PDF] J. Zhu, Y. Zhang, G. J. Joe, R. Pompetti, and S. G. Emerson NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal PNAS, August 16, 2005; 102(33): 11728 - 11733. [Abstract] [Full Text] [PDF] J. P. Chute, G. G. Muramoto, J. Fung, and C. Oxford Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38- cells and SCID-repopulating cells Blood, January 15, 2005; 105(2): 576 - 583. [Abstract] [Full Text] [PDF] K. Kirito, N. Fox, and K. Kaushansky Thrombopoietin Induces HOXA9 Nuclear Transport in Immature Hematopoietic Cells: Potential Mechanism by Which the Hormone Favorably Affects Hematopoietic Stem Cells Mol. Cell. Biol., August 1, 2004; 24(15): 6751 - 6762. [Abstract] [Full Text] [PDF]

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