title: Key role of flt3 ligand in regulation of the common lymphoid progenitor but not in maintenance of the hematopoietic stem cell pool.
abstract: 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.
authors.affiliation: 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
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.forename: Kim
authors.initials: K
authors.lastname: Theilgaard-Mönch
authors.forename: Natalija
authors.initials: N
authors.lastname: Buza-Vidas
authors.forename: Jörgen
authors.initials: J
authors.lastname: Adolfsson
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: 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
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein