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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4856-4865. Prepublished online as a Blood First Edition Paper on March 3, 2009; DOI 10.1182/blood-2008-09-181107. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-09-181107v1 113/20/4856    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 Wang, Z. Articles by Bunting, K. D. Search for Related Content PubMed PubMed Citation Articles by Wang, Z. Articles by Bunting, K. D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2008 Accepted February 26, 2009 Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient non-ablative stem cell replacement Zhengqi Wang, Geqiang Li, William Tse, and Kevin D. Bunting* Department of Medicine, Hematology-Oncology, Case Western Reserve University, Cleveland, OH, United States Center for Stem Cell and Regenerative Medicine, Cleveland, OH, United States Case Comprehensive Cancer Center, Cleveland, OH, United States * Corresponding author; email: kdb10{at}case.edu. Currently there is a major need in hematopoietic stem cell (HSC) transplantation to develop reduced intensity regimens that do not cause DNA damage and associated toxicities and that allow a wider range of patients to receive therapy. Cytokine receptor signals through c-Kit and c-Mpl can modulate HSC quiescence and engraftment but the intracellular signals and transcription factors that mediate these effects during transplantation have not been defined. Here we show that loss of one allele of signal transducer and activator of transcription 5 (STAT5) in non-ablated adult mutant mice permitted engraftment with wild-type HSC. Conditional deletion of STAT5 using Mx1-Cre caused maximal reduction in STAT5 mRNA (>97%) and rapidly decreased quiescence-associated c-Mpl downstream targets (Tie-2, p57), increased HSC cycling, and gradually reduced survival and depleted the long-term (LT)-HSC pool. Host deletion of STAT5 was persistent and permitted efficient donor LT-HSC engraftment in primary and secondary hosts in the absence of ablative conditioning. Overall, these studies establish proof-of-principle for targeting of STAT5 as novel transplantation conditioning and demonstrate for the first time that STAT5, a mitogenic factor in most cell types including hematopoietic progenitors, is a key transcriptional regulator that maintains quiescence of HSC during steady-state hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kimura, M. A. Rieger, J. M. Simone, W. Chen, M. C. Wickre, B.-M. Zhu, P. S. Hoppe, J. J. O'Shea, T. Schroeder, and L. Hennighausen The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis Blood, November 19, 2009; 114(21): 4721 - 4728. [Abstract] [Full Text] [PDF] L. E. Hays Heterogeneity in the AML stem cell pool Blood, November 5, 2009; 114(19): 3976 - 3977. [Full Text] [PDF] D. Yamaji, R. Na, Y. Feuermann, S. Pechhold, W. Chen, G. W. Robinson, and L. Hennighausen Development of mammary luminal progenitor cells is controlled by the transcription factor STAT5A Genes & Dev., October 15, 2009; 23(20): 2382 - 2387. [Abstract] [Full Text] [PDF]

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