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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2959-2967. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-07-2670. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2670v1 107/7/2959    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 Priestley, G. V. Articles by Papayannopoulou, T. Search for Related Content PubMed PubMed Citation Articles by Priestley, G. V. Articles by Papayannopoulou, T. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Lack of 4 integrin expression in stem cells restricts competitive function and self-renewal activity Gregory V. Priestley, Linda M. Scott, Tatiana Ulyanova, and Thalia Papayannopoulou From the Division of Hematology, University of Washington, Seattle, WA; and the University Department of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom. Alpha4 integrin or VLA4 (CD49d/CD29) is a multitask molecule with wide expression within and outside the hematopoietic system. Because targeted ablation of 4 integrin leads to embryonic lethality, to study its effects on adult hematopoiesis, we used animals with conditional excision of 4 integrin (4/) in hematopoietic cells. In such animals, we previously documented weakened bone marrow retention of progenitor cells during homeostasis and impaired homing and short-term engraftment after transplantation. In the present study we show that long-term repopulating cells lacking 4 integrins display a competitive disadvantage in hematopoietic reconstitution compared to normal competitors. Although initial dominance of 4+ competitors is due to their better homing and proliferative expansion early after transplantation, a progressive decline in contribution of 4/ hematopoiesis is compatible with neither normal homing nor normal function of 4/ hematopoietic stem cells (HSCs) in post-homing hematopoiesis. In the absence of 4+ competitor cells, 4/ HSCs can establish long-term hematopoiesis in primary recipients, however, some resurgence of host hematopoiesis is evident, and it becomes dominant in secondary transplants, so that no survivors with exclusively 4/ cells are seen in tertiary transplants. Collectively, our data provide compelling evidence that under regenerative stress 4 integrin assumes a greater importance than for maintenance of steady-state hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Ghiaur, M. J. Ferkowicz, M. D. Milsom, J. Bailey, D. Witte, J. A. Cancelas, M. C. Yoder, and D. A. Williams Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells Blood, April 1, 2008; 111(7): 3313 - 3321. [Abstract] [Full Text] [PDF] H. Qian, E. Georges-Labouesse, A. Nystrom, A. Domogatskaya, K. Tryggvason, S. E. W. Jacobsen, and M. Ekblom Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells Blood, October 1, 2007; 110(7): 2399 - 2407. [Abstract] [Full Text] [PDF] M. Magnusson, A. C. M. Brun, N. Miyake, J. Larsson, M. Ehinger, J. M. 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