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Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors.
Sitnicka, Ewa; Buza-Vidas, Natalija; Ahlenius, Henrik; Cilio, Corrado M; Gekas, Christos; Nygren, Jens M; Månsson, Robert; Cheng, Min; Jensen, Christina T; Svensson, Marcus; Leandersson, Karin; Agace, William W; Sigvardsson, Mikael; Jacobsen, Sten Eirik W.
Afiliação
  • Sitnicka E; Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Blood ; 110(8): 2955-64, 2007 Oct 15.
Article em En | MEDLINE | ID: mdl-17540845
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 alpha (IL-7Ralpha) 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-7Ralpha-independent fetal and adult T lymphopoiesis. Moreover, we establish a unique and critical role of FL, distinct from that of IL-7Ralpha, in regulation of the earliest lineage-negative (Lin(-)) Lin(-)SCA1+KIT+ (LSK) FLT3(hi) lymphoid-primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling in regulating the very earliest stages of lymphoid progenitors.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Linfócitos T / Receptores de Interleucina-7 / Linfopoese / Proteínas de Membrana Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2007 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Linfócitos T / Receptores de Interleucina-7 / Linfopoese / Proteínas de Membrana Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2007 Tipo de documento: Article