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 Blood, 9 April 2009, Vol. 113, No. 15, pp. 3453-3460.
Prepublished online as a Blood First Edition Paper on February 2, 2009; DOI 10.1182/blood-2008-08-174060.

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HEMATOPOIESIS AND STEM CELLS

FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells

Natalija Buza-Vidas1,2, Min Cheng1, Sara Duarte1,2, Hojjatollah Nozad Charoudeh1, Sten Eirik W. Jacobsen1,2,*, and Ewa Sitnicka1,*

1 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden; and 2 Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, United Kingdom

Originally cloned from hematopoietic stem cell (HSC) populations and its ligand being extensively used to promote ex vivo HSC expansion, the FMS-like tyrosine kinase 3 (FLT3; also called FLK2) receptor and its ligand (FL) were expected to emerge as an important physiologic regulator of HSC maintenance and expansion. However, the role of FLT3 receptor and ligand in HSC regulation remains unclear and disputed. Herein, using Fl-deficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Flk2–/– mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative ligands might potentially interact directly or indirectly with FLT3 receptor, we here also characterized HSCs in Flk2–/– mice. Advanced phenotypic as well as functional evaluation of Flk2–/– HSCs showed that the FLT3 receptor is dispensable for HSC steady-state maintenance and expansion after transplantation. Taken together, these studies show that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or posttransplantation expansion.


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