title: Human dendritic cells (DCs) are derived from distinct circulating precursors that are precommitted to become CD1c+ or CD141+ DCs.
abstract: In humans, conventional dendritic cells (cDCs) exist as two unique populations characterized by expression of CD1c and CD141. cDCs arise from increasingly restricted but well-defined bone marrow progenitors that include the common DC progenitor that differentiates into the pre-cDC, which is the direct precursor of cDCs. In this study, we show that pre-cDCs in humans are heterogeneous, consisting of two distinct populations of precursors that are precommitted to become either CD1c+or CD141+cDCs. The two groups of lineage-primed precursors can be distinguished based on differential expression of CD172a. Both subpopulations of pre-cDCs arise in the adult bone marrow and can be found in cord blood and adult peripheral blood. Gene expression analysis revealed that CD172a+and CD172a-pre-cDCs represent developmentally discrete populations that differentially express lineage-restricted transcription factors. A clinical trial of Flt3L injection revealed that this cytokine increases the number of both CD172a-and CD172a+pre-cDCs in human peripheral blood.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 gbreton@rockefeller.edu.
authors.forename: Gaëlle
authors.identifier: 0000-0003-3540-9378
authors.initials: G
authors.lastname: Breton
authors.affiliation: New York Genome Center, New York, NY 10013.|Center for Genomics and Systems Biology, New York University, New York, NY 10012.
authors.forename: Shiwei
authors.identifier: 0000-0001-6682-6743
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Laboratory of Computational Biology and Bioinformatics, Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo 01509-010, Brazil.
authors.forename: Renan
authors.identifier: 0000-0002-8402-3175
authors.initials: R
authors.lastname: Valieris
authors.affiliation: Laboratory of Computational Biology and Bioinformatics, Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo 01509-010, Brazil.
authors.forename: Israel
authors.identifier: 0000-0002-4687-1499
authors.initials: I
authors.lastname: Tojal da Silva
authors.affiliation: New York Genome Center, New York, NY 10013.|Center for Genomics and Systems Biology, New York University, New York, NY 10012.
authors.forename: Rahul
authors.initials: R
authors.lastname: Satija
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.|Howard Hughes Medical Institute, Chevy Chase, MD 20815.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000954:Antigens, Surface / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D018180:Thrombomodulin; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D000943:Antigens, Differentiation; D000954:Antigens, Surface; C437944:CD1C protein, human; D006023:Glycoproteins; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; C546931:THBD protein, human; D018180:Thrombomodulin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3