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Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Bifurcated Dendritic Cell Differentiation In Vitro From Murine Lineage Phenotype-Negative c-kit+ Bone Marrow Hematopoietic Progenitor Cells Yi Zhang, Akihisa Harada, Jian-bin Wang, Yan-yun Zhang, Shin-ichi Hashimoto, Makoto Naito, and Kouji Matsushima From the Department of Molecular Preventive Medicine and CREST, School of Medicine, The University of Tokyo, Tokyo; and The Second Department of Pathology, School of Medicine, Niigata University, Niigata, Japan. We have recently established the culture system to generate dendritic cells (DCs) from murine Linc-kit+ bone marrow hematopoietic progenitor cells (HPCs) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + tumor necrosis factor- (TNF-). We present here the identification of two DC precursor subsets originated from HPCs with the phenotype of CD11b/dullCD11c+ and CD11b+hiCD11c+ that develop independently at early time points (days 4 to 6) in the same culture conditions. Both of CD11b/dullCD11c+ and CD11b+hiCD11c+ precursors could differentiate at day 10 to 14 into CD11b/dullCD11c+ mature DCs with typical morphology, phenotype, and the ability to stimulate allogenic mixed leukocyte reaction (MLR). However, the endocytic capacity of fluorescein isothiocyanate-dextran was markedly reduced during the differentiation. CD11b/dullCD11c+ precursors expressed high levels of Ia, CD86, CD40, and E-cadherin molecules, but not c-fms transcript, and mature DCs derived from this precursor subset continue to express abundant E-cadherin antigen, a discernible marker for Langerhans cells. In contrast, CD11b+hiCD11c+ precursors expressed c-fms mRNA, but low levels of Ia, CD86, and E-cadherin, whereas CD40 was undetectable. CD11b/dullCD11c+ mature DCs differentiated from these precursors displayed abundant c-fms mRNA and nonspecific esterase activity. Interestingly, CD11b+hiCD11c+ precursors, but not CD11b/dullCD11c+ precursors, may be bipotent cells that can be induced by M-CSF to differentiate into macrophages. All of these results suggest that CD11b/dullCD11c+ and CD11b+hiCD11c+ cells are distinct DC precursors derived from Linc-kit+ HPCs, which differentiate into mature DCs through bifurcated and independent DC differentiation pathways. Blood, Vol. 92 No. 1 (July 1), 1998: pp. 118-128 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-J. Ko, J.-M. Lee, Y.-J. Kim, Y.-S. Kim, K.-A Lee, and C.-Y. Kang Immunosuppressive Myeloid-Derived Suppressor Cells Can Be Converted into Immunogenic APCs with the Help of Activated NKT Cells: An Alternative Cell-Based Antitumor Vaccine J. 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