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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4246-4254. Prepublished online as a Blood First Edition Paper on August 17, 2006; DOI 10.1182/blood-2006-02-005611. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-005611v1 108/13/4246    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 Blank, U. Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Blank, U. Articles by Karlsson, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 24, 2006 Accepted July 27, 2006 Smad7 promotes self-renewal of hematopoietic stem cells in vivo Ulrika Blank, Goran Karlsson, Jennifer L Moody, Taiju Utsugisawa, Mattias Magnusson, Sofie Singbrant, Jonas Larsson, and Stefan Karlsson* Molecular Medicine & Gene Therapy, Institute of Laboratory Medicine, Lund University, Lund, Sweden * Corresponding author; email: stefan.karlsson{at}med.lu.se. The Smad signaling pathway downstream of the Transforming Growth Factor- superfamily of ligands is an evolutionary conserved signaling circuitry with critical functions in a wide variety of biological processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here, that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary BM transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad signaling cascade in Smad7 overexpressing cells. Taken together, this data reveal an important and previously unappreciated role for the Smad signaling pathway in the regulation of self-renewal of HSCs in vivo. 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] B. Schiedlmeier, A. C. Santos, A. Ribeiro, N. Moncaut, D. Lesinski, H. Auer, K. Kornacker, W. Ostertag, C. Baum, M. Mallo, et al. HOXB4's road map to stem cell expansion PNAS, October 23, 2007; 104(43): 16952 - 16957. [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] 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]

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