Abstract
Abstract It has been known that the terminal differentiation of dendritic cells (DCs) takes place outside bone marrow (BM), although accumulation of DC precursors occurs in BM. However, cell 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 emergency myelopoiesis in vivo prevented DC differentiation by promoting accumulation of their precursors. Although both ligands activated Notch in hematopoietic progenitor cells (HPC), they had an opposite effect on Wnt signaling. Dll1 activated Wnt pathways; whereas, Jag1 inhibited it via down-regulation of the expression of Wnt receptors Frizzled (Fzd). Jag1 suppressed fzd expression by retaining histone deacetylase 1 in the complex with the transcription factor CSL/CBF-1 on fzd promoter. Our results suggest that DC differentiation, during emergency myelopoiesis, can be regulated by the nature of the Notch ligand expressed on adjacent stroma cells.
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