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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1208-1215. Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2006-01-010199. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-01-010199v1 108/4/1208    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 Chung, Y.-J. Articles by Oh, I.-H. Search for Related Content PubMed PubMed Citation Articles by Chung, Y.-J. Articles by Oh, I.-H. Related Collections Hematopoiesis and Stem Cells Signal Transduction Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Unique effects of Stat3 on the early phase of hematopoietic stem cell regeneration Yang-Jo Chung, Bo-Bae Park, Young-Ju Kang, Tae-min Kim, Connie J. Eaves, and Il-Hoan Oh From the Catholic Cell Therapy Center & Department of Cellular Medicine, Catholic University of Korea, Medical School, Seoul, Korea; and Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada. Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the signaling pathways that regulate this process remain poorly understood. Here we show that transduction of adult mouse bone marrow cells with a constitutively activated form of Stat3 (Stat3-C) increased their regenerative activity in lethally irradiated recipients. Conversely, transduction of these cells with a dominant-negative form of Stat3 suppressed their regenerative activity. Serial transplantation and clonal tracking of the HSC progeny regenerated in vivo from STAT3-C–transduced HSCs demonstrated that the major effect of forced expression of STAT3-C was to enhance HSC self-renewal during the initial phase of hematopoietic recovery. This acquired potential for enhanced self-renewal divisions then became latent, but was reactivated when the cells were transferred to new irradiated recipients. Increased levels of activated STAT3 were also found to be associated with greater preservation of primitive hematopoietic cells in short-term cultures. These results indicate a novel biphasic regulation of HSC self-renewal in vivo in which activated STAT3 promotes HSC self-renewal under stimulated, but not homeostatic, conditions. STAT3 may thus be an important regulator of hematopoietic regeneration and a novel target for HSC engineering. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. G. Kent, B. J. Dykstra, J. Cheyne, E. Ma, and C. J. Eaves Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells Blood, August 1, 2008; 112(3): 560 - 567. [Abstract] [Full Text] [PDF] D. Kent, M. Copley, C. Benz, B. Dykstra, M. Bowie, and C. Eaves Regulation of Hematopoietic Stem Cells by the Steel Factor/KIT Signaling Pathway Clin. Cancer Res., April 1, 2008; 14(7): 1926 - 1930. [Abstract] [Full Text] [PDF] B. Li, N. Jia, D. L. Waning, F.-C. Yang, L. S. Haneline, and K. T. Chun Cul4A is required for hematopoietic stem-cell engraftment and self-renewal Blood, October 1, 2007; 110(7): 2704 - 2707. [Abstract] [Full Text] [PDF] F. Zhang, S. I. Thornhill, S. J. Howe, M. Ulaganathan, A. Schambach, J. Sinclair, C. Kinnon, H. B. Gaspar, M. Antoniou, and A. J. Thrasher Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells Blood, September 1, 2007; 110(5): 1448 - 1457. [Abstract] [Full Text] [PDF] B. J. Jenkins, A. W. Roberts, C. J. Greenhill, M. Najdovska, T. Lundgren-May, L. Robb, D. Grail, and M. Ernst Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis Blood, March 15, 2007; 109(6): 2380 - 2388. [Abstract] [Full Text] [PDF]

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