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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3129-3135. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-04-1300. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1300v1 102/9/3129    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 Larsson, J. Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Larsson, J. Articles by Karlsson, S. Related Collections Hematopoiesis and Stem Cells Transplantation Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS TGF- signaling–deficient hematopoietic stem cells have normal self-renewal and regenerative ability in vivo despite increased proliferative capacity in vitro Jonas Larsson, Ulrika Blank, Hildur Helgadottir, Jon Mar Björnsson, Mats Ehinger, Marie-José Goumans, Xiaolong Fan, Per Levéen, and Stefan Karlsson From the Department of Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund University Hospital, Lund, Sweden; Department of Pathology, Lund University Hospital, Lund, Sweden; and Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Studies in vitro implicate transforming growth factor (TGF-) as a key regulator of hematopoiesis with potent inhibitory effects on progenitor and stem cell proliferation. In vivo studies have been hampered by early lethality of knock-out mice for TGF- isoforms and the receptors. To directly assess the role of TGF- signaling for hematopoiesis and hematopoietic stem cell (HSC) function in vivo, we generated a conditional knock-out model in which a disruption of the TGF- type I receptor (TRI) gene was induced in adult mice. HSCs from induced mice showed increased proliferation recruitment when cultured as single cells under low stimulatory conditions in vitro, consistent with an inhibitory role of TGF- in HSC proliferation. However, induced TRI null mice show normal in vivo hematopoiesis with normal numbers and differentiation ability of hematopoietic progenitor cells. Furthermore HSCs from TRI null mice exhibit a normal cell cycle distribution and do not differ in their ability long term to repopulate primary and secondary recipient mice following bone marrow transplantation. These findings challenge the classical view that TGF- is an essential negative regulator of hematopoietic stem cells under physiologic conditions in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Karlsson Is TGF-{beta} a stemness regulator? Blood, February 5, 2009; 113(6): 1208 - 1208. [Full Text] [PDF] S. Yamazaki, A. Iwama, S.-i. Takayanagi, K. Eto, H. Ema, and H. Nakauchi TGF-{beta} as a candidate bone marrow niche signal to induce hematopoietic stem cell hibernation Blood, February 5, 2009; 113(6): 1250 - 1256. [Abstract] [Full Text] [PDF] S. Avagyan, L. Glouchkova, J. Choi, and H.-W. Snoeck A Quantitative Trait Locus on Chromosome 4 Affects Cycling of Hematopoietic Stem and Progenitor Cells through Regulation of TGF-{beta}2 Responsiveness J. Immunol., November 1, 2008; 181(9): 5904 - 5911. [Abstract] [Full Text] [PDF] U. Blank, G. Karlsson, and S. Karlsson Signaling pathways governing stem-cell fate Blood, January 15, 2008; 111(2): 492 - 503. [Abstract] [Full Text] [PDF] D. H. Kaplan, M. O. Li, M. C. Jenison, W. D. Shlomchik, R. A. Flavell, and M. J. Shlomchik Autocrine/paracrine TGF{beta}1 is required for the development of epidermal Langerhans cells J. Exp. Med., October 29, 2007; 204(11): 2545 - 2552. [Abstract] [Full Text] [PDF] D. Pan, T. Schomber, C. P. Kalberer, L. M. Terracciano, K. Hafen, W. Krenger, H. Hao-Shen, C. Deng, and R. C. Skoda Normal erythropoiesis but severe polyposis and bleeding anemia in Smad4-deficient mice Blood, October 15, 2007; 110(8): 3049 - 3055. [Abstract] [Full Text] [PDF] M. Magnusson, A. C. M. Brun, N. Miyake, J. Larsson, M. Ehinger, J. M. Bjornsson, A. Wutz, M. Sigvardsson, and S. Karlsson HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development Blood, May 1, 2007; 109(9): 3687 - 3696. [Abstract] [Full Text] [PDF] G. Karlsson, U. Blank, J. L. Moody, M. Ehinger, S. Singbrant, C.-X. Deng, and S. Karlsson Smad4 is critical for self-renewal of hematopoietic stem cells J. Exp. Med., March 19, 2007; 204(3): 467 - 474. [Abstract] [Full Text] [PDF] U. Blank, G. Karlsson, J. L. Moody, T. Utsugisawa, M. Magnusson, S. Singbrant, J. Larsson, and S. Karlsson Smad7 promotes self-renewal of hematopoietic stem cells Blood, December 15, 2006; 108(13): 4246 - 4254. [Abstract] [Full Text] [PDF] S. Singbrant, J. L. Moody, U. Blank, G. Karlsson, L. Umans, A. Zwijsen, and S. Karlsson Smad5 is dispensable for adult murine hematopoiesis Blood, December 1, 2006; 108(12): 3707 - 3712. [Abstract] [Full Text] [PDF] I. B. Enquist, E. Nilsson, A. Ooka, J.-E. Mansson, K. Olsson, M. Ehinger, R. O. Brady, J. Richter, and S. Karlsson Effective cell and gene therapy in a murine model of Gaucher disease PNAS, September 12, 2006; 103(37): 13819 - 13824. [Abstract] [Full Text] [PDF] M. Dong and G. C. Blobe Role of transforming growth factor-beta in hematologic malignancies Blood, June 15, 2006; 107(12): 4589 - 4596. [Abstract] [Full Text] [PDF] L. Li and W. B. Neaves Normal Stem Cells and Cancer Stem Cells: The Niche Matters. Cancer Res., May 1, 2006; 66(9): 4553 - 4557. [Abstract] [Full Text] [PDF] P. Leveen, M. Carlsen, A. Makowska, S. Oddsson, J. Larsson, M.-J. Goumans, C. M. Cilio, and S. Karlsson TGF-{beta} type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo Blood, December 15, 2005; 106(13): 4234 - 4240. [Abstract] [Full Text] [PDF]

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