Submitted August 13, 2008
Accepted December 19, 2008
FLT3 receptor and ligand are dispensable for maintenance and post-transplantation expansion of mouse hematopoietic stem cells
Natalija Buza-Vidas, Min Cheng, Sara Duarte, Hojjatollah Nozad Charoudeh, Sten Eirik W. Jacobsen*, and Ewa Sitnicka
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
* Corresponding author; email: sten.jacobsen{at}imm.ox.ac.uk.
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), was expected to emerge as an important physiological 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 post-transplantation is FL-independent. As previous findings in Flk2-/- mice were compatible with an important role of FLT3 receptor in HSC regulation, and as 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, demonstrated that also the FLT3 receptor is dispensable for HSC steady state maintenance and expansion post-transplantation. Taken together, these studies demonstrate that the FLT3 receptor and ligand are not critical regulators of mouse HSCs, neither in steady state nor during fetal or post-transplantation expansion.
