Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool.
The first lineage commitment step of hematopoietic stem cells (HSC) results in separation into distinct lymphoid and myeloid differentiation pathways, reflected in the generation of common lymphoid and myeloid progenitors (CLP and CMP, respectively). In this report we present the first evidence for a nonredundant regulator of this process, in that adult mice deficient in expression of the flt3 ligand (FL) have severely (10-fold) reduced levels of the CLP, accompanied by reductions in the earliest identifiable B and T cell progenitors. In contrast, CMP and HSC are unaffected in FL-deficient mice. Noteworthy, CLP express high levels of both the flt3 receptor and ligand, indicating a potential autocrine role of FL in regulation of the earliest lymphoid commitment step from HSC.
Sitnicka
Ewa
E
Department of Stem Cell Biology, Institute of Laboratory Medicine, University Hospital of Lund, BMC, B12, Klinikgatan 26, 221-84 Lund, Sweden. ewa.sitnicka@stemcell.lu.se
Bryder
David
D
Theilgaard-Mönch
Kim
K
Buza-Vidas
Natalija
N
Adolfsson
Jörgen
J
Jacobsen
Sten Eirik W
SE
D000818:Animals; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008024:Ligands; D038041:Lymphopoiesis / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038042:Myelopoiesis / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology / Q000502:physiology
D008024:Ligands; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein