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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2965-2972. Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-08-2963. This Article Full Text (PDF) All Versions of this Article: 2003-08-2963v1 103/8/2965    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 Bradley, H. L Articles by Bunting, K. D Search for Related Content PubMed PubMed Citation Articles by Bradley, H. L Articles by Bunting, K. D Social Bookmarking                   What's this? Submitted August 28, 2003 Accepted December 17, 2003 Hematopoietic repopulating defects from STAT5-deficient bone marrow are not fully accounted for by loss of thrombopoietin responsiveness Heath L Bradley, Christine Couldrey, and Kevin D Bunting* Hematopoiesis Department, American Red Cross Jerome H. Holland Laboratory for the Biomedical Sciences, Rockville, MD, USA Hematopoiesis Department, American Red Cross Jerome H. Holland Laboratory for the Biomedical Sciences, Rockville, MD, USA; Department of Anatomy and Cell Biology, The George Washington University, Washington, DC, USA * Corresponding author; email: buntingk{at}usa.redcross.org. Signal transducer and activator of transcription-5 (STAT5) plays an important role in repopulating activity of hematopoietic stem cells (HSCs). However, the relationship of STAT5 activation with early-acting cytokine receptors is not well established. We have directly compared bone marrow (BM) from mice mutant for STAT5a and STAT5b (STAT5ab-/-) with that from mice lacking c-Mpl (c-Mpl-/-), the thrombopoietin receptor. Both STAT5 and c-Mpl deficiency only mildly affected committed myeloid progenitors assayed in vitro, but STAT5ab-/- BM showed lower Gr-1+ (4.4-fold), B220+ (23-fold), CD4+ (20-fold), and Ter119+ (17-fold) peripheral blood repopulating activity than c-Mpl-/- BM against wild-type competitor in long-term repopulating assays in vivo. Direct head-to-head competitions of STAT5ab-/- BM and c-Mpl-/- BM showed up to a 25-fold reduction in STAT5ab-/- contribution. Differences affecting reconstitution of primitive c-Kit+Lin-Sca-1+ multipotent progenitor (MPP)/HSC (1.8-fold) and c-Kit+Lin-Sca-1- oligopotent progenitor BM fractions (3.3-fold) were more modest. In serial transplant experiments, STAT5ab-/- and c-Mpl-/- BM both failed to provide consistent engraftment in tertiary hosts and could not radioprotect lethally-irradiated quaternary recipients. These results indicate substantial overlap in c-Mpl-STAT5 signaling defects at the MPP/HSC level but indicate that STAT5 is activated independent of c-Mpl to promote multilineage hematopoietic differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Wang, G. Li, W. Tse, and K. D. Bunting Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement Blood, May 14, 2009; 113(20): 4856 - 4865. [Abstract] [Full Text] [PDF] A. T. J. Wierenga, E. Vellenga, and J. J. Schuringa Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels Mol. Cell. Biol., November 1, 2008; 28(21): 6668 - 6680. [Abstract] [Full Text] [PDF] F. Grebien, M. A. Kerenyi, B. Kovacic, T. Kolbe, V. Becker, H. Dolznig, K. Pfeffer, U. Klingmuller, M. Muller, H. Beug, et al. Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2 Blood, May 1, 2008; 111(9): 4511 - 4522. [Abstract] [Full Text] [PDF] M. A. Weinreich, I. Lintmaer, L. Wang, H. D. Liggitt, M. A. Harkey, and C. A. Blau Growth factor receptors as regulators of hematopoiesis Blood, December 1, 2006; 108(12): 3713 - 3721. [Abstract] [Full Text] [PDF] D. Ye, N. Wolff, L. Li, S. Zhang, and R. L. Ilaria Jr STAT5 signaling is required for the efficient induction and maintenance of CML in mice Blood, June 15, 2006; 107(12): 4917 - 4925. [Abstract] [Full Text] [PDF] Y. Kato, A. Iwama, Y. Tadokoro, K. Shimoda, M. Minoguchi, S. Akira, M. Tanaka, A. Miyajima, T. Kitamura, and H. Nakauchi Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis J. Exp. Med., July 5, 2005; 202(1): 169 - 179. [Abstract] [Full Text] [PDF] C. Couldrey, H. L. Bradley, and K. D. Bunting A STAT5 modifier locus on murine chromosome 7 modulates engraftment of hematopoietic stem cells during steady-state hematopoiesis Blood, February 15, 2005; 105(4): 1476 - 1483. [Abstract] [Full Text] [PDF]

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