title: Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
abstract: Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H(-)Ly6C(-) pre-DCs) or cDC2 lineage (Siglec-H(-)Ly6C(+) pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: V
authors.initials: V
authors.lastname: Sivakamasundari
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Jinmiao
authors.identifier: 0000000175476423
authors.initials: J
authors.lastname: Chen
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Hermi Rizal Bin
authors.initials: HR
authors.lastname: Sumatoh
authors.affiliation: Molecular Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Jaring
authors.initials: J
authors.lastname: Schreuder
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lum
authors.affiliation: 1] Singapore Immunology Network, Agency for Science, Technology and Research, Singapore. [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Sanqian
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Laurent
authors.identifier: 0000000303491557
authors.initials: L
authors.lastname: Renia
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Michael
authors.identifier: 0000000210472277
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: 1] Molecular Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. [2] Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Shalin
authors.initials: S
authors.lastname: Naik
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Evan W
authors.identifier: 000000022889243X
authors.initials: EW
authors.lastname: Newell
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Paul
authors.identifier: 0000000201913958
authors.initials: P
authors.lastname: Robson
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
authors.forename: Florent
authors.identifier: 0000000228577755
authors.initials: F
authors.lastname: Ginhoux
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000950:Antigens, Ly; D039481:CD11b Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D039001:Integrin alpha Chains; D037102:Lectins; C494192:Ly-6C antigen, mouse; D011956:Receptors, Cell Surface; C510552:Siglech protein, mouse; C091367:alpha E integrins