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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.

Original publication

DOI

10.1182/blood-2006-10-054726

Type

Journal article

Journal

Blood

Publication Date

15/10/2007

Volume

110

Pages

2955 - 2964

Keywords

Animals, B-Lymphocytes, Base Sequence, Bone Marrow Cells, Cell Differentiation, Fetus, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression, Hematopoietic Stem Cells, Image Processing, Computer-Assisted, Lymphopoiesis, Membrane Proteins, Mice, Molecular Sequence Data, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Receptors, Interleukin-7, T-Lymphocytes, Thymus Gland