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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1905-1915. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-03-0881. This Article Full Text (PDF) All Versions of this Article: 2004-03-0881v1 105/5/1905    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 Chadwick, K. Articles by Bhatia, M. Search for Related Content PubMed PubMed Citation Articles by Chadwick, K. Articles by Bhatia, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 8, 2004 Accepted September 30, 2004 Smad7 alters cell fate decisions of human hematopoietic repopulating cells Kristin Chadwick, Farbod Shojaei, Lisa Gallacher, and Mickie Bhatia* Robarts Research Institute, Krembil Centre for Stem Cell Biology, London, ON, Canada; Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada Robarts Research Institute, Krembil Centre for Stem Cell Biology, London, ON, Canada * Corresponding author; email: mbhatia{at}robarts.ca. Intracellular SMAD proteins mediate signal transduction of the Transforming Growth Factor-b (TGF-) superfamily that play pleiotropic roles in hematopoietic development, suggesting that intracellular Smad proteins may play key roles in hematopoietic regulation. Although inhibitory Smad7, which negatively regulates TGF- signaling, has been implicated in the development of mature hematopoietic cells, a role for Smad7 in regulating more primitive hematopoietic cells has yet to be examined. Here, Smad7 was over-expressed in primary human SCID repopulating cells (SRC), representing a common myeloid/lymphoid precursor cell with the functional capacity to repopulate the bone marrow of NOD/SCID recipient mice. Retroviral transduction of Smad7 into human umbilical cord blood (CB)-SRC caused a shift from lymphoid dominant engraftment toward increased myeloid contribution, and increased the myeloid-committed clonogenic progenitor frequency in reconstituted mice. Neither myeloid nor B-lymphoid lineage developmental stages were compromised by Smad7 overexpression, suggesting Smad7 regulates cell fate commitment decisions of myeloid/lymphoid precursors by augmenting myeloid differentiation at the expense of lymphoid commitment. In addition, global gene expression analysis using microarray was used to identify potential target genes regulated by SMAD7 in primitive hematopoietic cells that may control this process. Our study demonstrates a novel and unexpected role for Smad7 in modulating the cell fate decisions of primary multipotent human repopulating cells and establishes a role for Smad7 in the development of primitive human hematopoietic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] C. Wang, P. W. Faloon, Z. Tan, Y. Lv, P. Zhang, Y. Ge, H. Deng, and J.-W. Xiong Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation Blood, November 15, 2007; 110(10): 3601 - 3609. [Abstract] [Full Text] [PDF] J. E. Pimanda, I. J. Donaldson, M. F. T. R. de Bruijn, S. Kinston, K. Knezevic, L. Huckle, S. Piltz, J.-R. Landry, A. R. Green, D. Tannahill, et al. The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity PNAS, January 16, 2007; 104(3): 840 - 845. [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] L. Mishra, R. Derynck, and B. Mishra Transforming Growth Factor-{beta} Signaling in Stem Cells and Cancer Science, October 7, 2005; 310(5745): 68 - 71. [Abstract] [Full Text] [PDF] C. M. Mallawaarachchi, P. L. Weissberg, and R. C.M. Siow Smad7 Gene Transfer Attenuates Adventitial Cell Migration and Vascular Remodeling After Balloon Injury Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1383 - 1387. [Abstract] [Full Text] [PDF] L. Wang, P. Menendez, F. Shojaei, L. Li, F. Mazurier, J. E. Dick, C. Cerdan, K. Levac, and M. Bhatia Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic HOXB4 expression J. Exp. Med., May 16, 2005; 201(10): 1603 - 1614. [Abstract] [Full Text] [PDF]

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