SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2002-07-2099. This Article Full Text (PDF) All Versions of this Article: 2002-07-2099v1 102/4/1282    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 Lacout, C. Articles by Dumenil, D. Search for Related Content PubMed PubMed Citation Articles by Lacout, C. Articles by Dumenil, D. Social Bookmarking                   What's this? Submitted July 15, 2002 Accepted April 11, 2003 A defect in hematopoietic stem cell migration explains the non-random X-chromosome inactivation in carriers of Wiskott-Aldrich syndrome Catherine Lacout, Elie Haddad, Siham Sabri, Fedor Svinarchouk, Loic Garcon, Claude Capron, Adlan Foudi, Rym Mzali, Scott B Snapper, Fawzia Louache, William Vainchenker, and Dominique Dumenil* Institut Gustave Roussy, Unite 362, INSERM, Villejuif, France Faculte Pharmacie, Unite 461, INSERM, Chatenay Mallabry, France Departments of Medecine, Gatrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA * Corresponding author; email: domdum{at}igr.fr. A defect in cell trafficking and chemotaxis plays an important role in the immune deficiency observed in the Wiskott-Aldrich syndrome (WAS). In this report, we show that marrow cells from WASP deficient mice have also a defect in chemotaxis. Serial transplantation and competitive reconstitution experiments demonstrated that marrow cells, including hematopoietic progenitors and stem cells (HSC), have decrease homing capacities which were associated to a defect in adhesion to collagen. During development, HSC migrate from the liver to the marrow and the spleen, prompting us to ask if a defect in HSC homing during development may explain the skewed X-chromosome inactivation in WAS carriers. Preliminary evidence has shown that, in contrast to marrow progenitor cells, fetal liver progenitor cells from heterozygous female had a random X-chromosome inactivation. When fetal liver cells from WASP carrier female were injected into irradiated recipients, a non random inactivation of the X-chromosome was found at the level of hematopoietic progenitors and HSC responsible for the short and long term hematopoietic reconstitution. Therefore, the mechanism of the skewed X-chromosomal inactivation observed in WAS carriers may be related to a migration defect of WASP-deficient HSC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mani, S. Venkatasubrahmanyam, M. Sanyal, S. Levy, A. Butte, K. Weinberg, and T. Jahn Wiskott-Aldrich syndrome protein is an effector of Kit signaling Blood, October 1, 2009; 114(14): 2900 - 2908. [Abstract] [Full Text] [PDF] M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, and M. Grazia Roncarolo Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome Blood, June 18, 2009; 113(25): 6288 - 6295. [Abstract] [Full Text] [PDF] A. Astrakhan, H. D. Ochs, and D. J. Rawlings Wiskott-Aldrich Syndrome Protein Is Required for Homeostasis and Function of Invariant NKT Cells J. Immunol., June 15, 2009; 182(12): 7370 - 7380. [Abstract] [Full Text] [PDF] L. D. Notarangelo and R. Badolato Leukocyte trafficking in primary immunodeficiencies J. Leukoc. Biol., March 1, 2009; 85(3): 335 - 343. [Abstract] [Full Text] [PDF] A. Meyer-Bahlburg, S. Becker-Herman, S. Humblet-Baron, S. Khim, M. Weber, G. Bouma, A. J. Thrasher, F. D. Batista, and D. J. Rawlings Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis Blood, November 15, 2008; 112(10): 4158 - 4169. [Abstract] [Full Text] [PDF] L. S. Westerberg, M. A. de la Fuente, F. Wermeling, H. D. Ochs, M. C. I. Karlsson, S. B. Snapper, and L. D. Notarangelo WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function Blood, November 15, 2008; 112(10): 4139 - 4147. [Abstract] [Full Text] [PDF] V. Cotta-de-Almeida, L. Westerberg, M. H. Maillard, D. Onaldi, H. Wachtel, P. Meelu, U.-i. Chung, R. Xavier, F. W. Alt, and S. B. Snapper Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development PNAS, September 25, 2007; 104(39): 15424 - 15429. [Abstract] [Full Text] [PDF] K. M. Eisenmann, R. A. West, D. Hildebrand, S. M. Kitchen, J. Peng, R. Sigler, J. Zhang, K. A. Siminovitch, and A. S. Alberts T Cell Responses in Mammalian Diaphanous-related Formin mDia1 Knock-out Mice J. Biol. Chem., August 24, 2007; 282(34): 25152 - 25158. [Abstract] [Full Text] [PDF] S. Sabri, A. Foudi, S. Boukour, B. Franc, S. Charrier, M. Jandrot-Perrus, R. W. Farndale, A. Jalil, M. P. Blundell, E. M. Cramer, et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment Blood, July 1, 2006; 108(1): 134 - 140. [Abstract] [Full Text] [PDF] T. Neff, B. C. Beard, and H.-P. Kiem Survival of the fittest: in vivo selection and stem cell gene therapy Blood, March 1, 2006; 107(5): 1751 - 1760. [Abstract] [Full Text] [PDF] L. Wang, L. Yang, M.-D. Filippi, D. A. Williams, and Y. Zheng Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment Blood, January 1, 2006; 107(1): 98 - 105. [Abstract] [Full Text] [PDF] S. B. Snapper, P. Meelu, D. Nguyen, B. M. Stockton, P. Bozza, F. W. Alt, F. S. Rosen, U. H. von Andrian, and C. Klein WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo J. Leukoc. Biol., June 1, 2005; 77(6): 993 - 998. [Abstract] [Full Text] [PDF] S. de Noronha, S. Hardy, J. Sinclair, M. P. Blundell, J. Strid, O. Schulz, J. Zwirner, G. E. Jones, D. R. Katz, C. Kinnon, et al. Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein Blood, February 15, 2005; 105(4): 1590 - 1597. [Abstract] [Full Text] [PDF] L. Westerberg, M. Larsson, S. J. Hardy, C. Fernandez, A. J. Thrasher, and E. Severinson Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response Blood, February 1, 2005; 105(3): 1144 - 1152. [Abstract] [Full Text] [PDF] S. Burns, G. O. Cory, W. Vainchenker, and A. J. Thrasher Mechanisms of WASp-mediated hematologic and immunologic disease Blood, December 1, 2004; 104(12): 3454 - 3462. [Abstract] [Full Text] [PDF] T. Papayannopoulou Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization Blood, March 1, 2004; 103(5): 1580 - 1585. [Abstract] [Full Text] [PDF] T. S. Strom, S. J. Turner, S. Andreansky, H. Liu, P. C. Doherty, D. K. Srivastava, J. M. Cunningham, and A. W. Nienhuis Defects in T-cell-mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells Blood, November 1, 2003; 102(9): 3108 - 3116. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020