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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2955-2964. Prepublished online as a Blood First Edition Paper on May 31, 2007; DOI 10.1182/blood-2006-10-054726. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-10-054726v1 110/8/2955    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 Sitnicka, E. Articles by Jacobsen, S. E. W Search for Related Content PubMed PubMed Citation Articles by Sitnicka, E. Articles by Jacobsen, S. E. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 26, 2006 Accepted May 28, 2007 Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors Ewa Sitnicka, Natalija Buza-Vidas, Henrik Ahlenius, Corrado M Cilio, Christos Gekas, Jens M Nygren, Robert Mansson, Min Cheng, Christina T Jensen, Marcus Svensson, Karin Leandersson, William W Agace, Mikael Sigvardsson, and Sten Eirik W Jacobsen* Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden Department of Clinical Sciences & Department of Paediatrics, Cellular Autoimmunity Unit, Malmo University Hospital, Malmo, Sweden Immunology Section, Department of Cell & Molecular Biology, Lund University, Lund, Sweden Experimental Pathology, Malmo University Hospital, Malmo, Sweden * Corresponding author; email: sten.jacobsen{at}med.lu.se. The molecular pathways regulating lymphoid priming, fate and development of multipotent bone marrow (BM) stem/progenitor cells that continuously replace thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine kinase 3 (FLT3) ligand (FL) deficient mice have distinct reductions in the earliest thymic progenitors in fetal, postnatal and adult thymus. A critical role of FL in thymopoiesis was particularly evident in the absence of interleukin-7 receptor (IL-7R) signaling. FL-/-IL-7R-/- mice have extensive reductions in fetal and postnatal thymic progenitors that result in a loss of active thymopoiesis in adult mice, demonstrating an indispensable role of FL in IL-7R-independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7R, in regulation of the earliest lineage negative (Lin-) Lin-SCA-1+C-KIT+(LSK)FLT3hi lymphoid-primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. T. Jensen, C. Boiers, S. Kharazi, A. Lubking, T. Ryden, M. Sigvardsson, E. Sitnicka, and S. E. W. Jacobsen Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development Blood, February 15, 2008; 111(4): 2083 - 2090. [Abstract] [Full Text] [PDF]

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