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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 6, 2005 Accepted November 20, 2005 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* Medicine/Div. of Hematology, University of Washington, Seattle, WA, USA Univ. Dept. of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom * Corresponding author; email: thalp{at}u.washington.edu. 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 post-transplantation. In the present study we show that long-term repopulating cells lacking 4 integrins display a competitive disadvantage in hemopoietic reconstitution compared to normal competitors. Although initial dominance of 4+ competitors is due to their better homing and proliferative expansion early post-transplantation, a progressive decline in contribution of 4/ hematopoiesis is compatible neither with normal homing nor normal function of 4/ 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 2° transplants, so that no survivors with exclusively 4/ cells are seen in 3° transplants. 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