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Critical role of FLT3 ligand in IL-7 receptor-independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
Department of Clinical Sciences, Cellular Autoimmunity Unit, Malmö University Hospital, Malmö, Sweden.
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2007 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 110, no 8, p. 2955-2964Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Washington, DC: American Society of Hematology , 2007. Vol. 110, no 8, p. 2955-2964
Keywords [en]
hematopoietic stem-cells, interleukin-7 receptor, deficient mice, c-kit, bone-marrow, lineage progenitors, thymic emigrants, in-vivo, differentiation, expression
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hh:diva-15172DOI: 10.1182/blood-2006-10-054726ISI: 000250426700034PubMedID: 17540845Scopus ID: 2-s2.0-35548939080OAI: oai:DiVA.org:hh-15172DiVA, id: diva2:419609
Available from: 2011-05-27 Created: 2011-05-27 Last updated: 2017-12-11Bibliographically approved

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