title: Regulation of dendritic cell differentiation in bone marrow during emergency myelopoiesis.
abstract: Although accumulation of dendritic cell (DC) precursors occurs in bone marrow, the terminal differentiation of these cells takes place outside bone marrow. The signaling, regulating this process, remains poorly understood. We demonstrated that this process could be differentially regulated by Notch ligands: Jagged-1 (Jag1) and Delta-like ligand 1 (Dll1). In contrast to Dll1, Jag1, in vitro and during induced myelopoiesis in vivo, prevented DC differentiation by promoting the accumulation of their precursors. Although both ligands activated Notch in hematopoietic progenitor cells, they had an opposite effect on Wnt signaling. Dll1 activated Wnt pathways, whereas Jag1 inhibited it via downregulation of the expression of the Wnt receptors Frizzled (Fzd). Jag1 suppressed fzd expression by retaining histone deacetylase 1 in the complex with the transcription factor CSL/CBF-1 on the fzd promoter. Our results suggest that DC differentiation, during induced myelopoiesis, can be regulated by the nature of the Notch ligand expressed on adjacent stroma cells.
authors.affiliation: Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Pingyan
authors.initials: P
authors.lastname: Cheng
authors.forename: Indu
authors.initials: I
authors.lastname: Ramachandran
authors.forename: Yulia
authors.initials: Y
authors.lastname: Nefedova
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Gabrilovich
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D020296:Animals, Congenic; D001854:Bone Marrow Cells; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology*; D015536:Down-Regulation; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D056284:Histone Deacetylase 1 / Q000502:physiology; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000502:physiology; D000072100:Jagged-1 Protein; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D038042:Myelopoiesis / Q000187:drug effects / Q000502:physiology*; D011070:Poly I-C / Q000494:pharmacology; D034622:RNA Interference; D011828:Radiation Chimera; D051881:Receptor, Notch1 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D017154:Stromal Cells / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000172:deficiency / Q000502:physiology
chemical_list: C495267:CTNNB1 protein, mouse; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D051157:Frizzled Receptors; C492388:Fzd10 protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C497762:Notch1 protein, mouse; C497571:Rbpj protein, mouse; D051881:Receptor, Notch1; D011993:Recombinant Fusion Proteins; D000072099:Serrate-Jagged Proteins; D051176:beta Catenin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D011070:Poly I-C