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

Abstract

Originally cloned from hematopoietic stem cell (HSC) populations and its li- gand being extensively used to promote ex vivo HSC expansion, the FMS-like ty- rosine 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 FI Adeficient mice, we establish for the first time that HSC expansion in fetal liver and after transplantation is FL independent. Because previous findings in Fik2-/-mice were compatible with an important role of FLT3 receptor in HSC regulation and because alternative li- gands 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 Fik2-/- 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. © 2009 by The American Society of Hematology.