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Blood, 15 January 2009, Vol. 113, No. 3, pp. 546-554. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-06-163774. This Article Full Text (PDF) All Versions of this Article: blood-2008-06-163774v1 113/3/546    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 Luis, T. C Articles by Staal, F. J. Search for Related Content PubMed PubMed Citation Articles by Luis, T. C Articles by Staal, F. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 18, 2008 Accepted September 8, 2008 Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation Tiago C Luis, Floor Weerkamp, Brigitta AE Naber, Miranda RM Baert, Edwin FE de Haas, Tatjana Nikolic, Sjanneke Heuvelmans, Ronald R De Krijger, Jacques JM van Dongen, and Frank JT Staal* Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands Department of Pulmonary medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands Department of Pathology, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands * Corresponding author; email: f.staal{at}erasmusmc.nl. Canonical Wnt signaling has been implicated in various aspects of hematopoiesis. Its role is controversial due to different outcomes between various inducible Wnt signaling loss-of-function models and also compared to gain-of-function systems. We therefore studied a mouse deficient for a Wnt gene that seemed to play a non-redundant role in hematopoiesis. Mice lacking Wnt3a die prenatally around E12.5, allowing fetal hematopoiesis to be studied using in vitro assays and transplantation into irradiated recipient mice. Here we show that Wnt3a deficiency leads to a reduction in the numbers of hematopoietic stem cells (HSC) and progenitor cells in the fetal liver (FL) and to severely reduced reconstitution capacity as measured in secondary transplantation assays. This deficiency is irreversible and cannot be restored by transplantation into Wnt3a competent mice. The impaired long-term repopulation capacity of Wnt3a-/- HSCs could not be explained by altered cell cycle or survival of primitive progenitors. Moreover, Wnt3a deficiency affected myeloid but not B-lymphoid development at the progenitor level, and affected immature thymocyte differentiation. Our results show that Wnt3a signaling not only provides proliferative stimuli, such as for immature thymocytes, but also regulates cell fate decisions of HSC during hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. D. Boudoulas and A. K. Hatzopoulos Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease Dis. Model. Mech., July 1, 2009; 2(7-8): 344 - 358. [Abstract] [Full Text] [PDF]

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