title: Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic cell development from common dendritic cell progenitors.
abstract: Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c+MHCII-precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking. Analysis of CDP genealogies revealed a stepwise differentiation of CDPs into pDCs in a part of the CDP colonies. This developmental pathway involved an early CD11c+SiglecH-pre-DC stage and a Siglec H+CCR9lowprecursor stage, which was followed rapidly by upregulation of CCR9 indicating final pDC differentiation. In the majority of the remaining CDP pedigrees however the Siglec H+CCR9lowprecursor state was maintained for several generations. Thus, although a fraction of CDPs transits through precursor stages rapidly to give rise to a first wave of pDCs, the majority of CDP progeny differentiate more slowly and give rise to longer lived precursor cells which are poised to differentiate on demand.
authors.affiliation: Institute for Immunology, Biomedical Center, Ludwig-Maximilians-University Munich, Großhaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Dursun
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Max
authors.initials: M
authors.lastname: Endele
authors.affiliation: Institute for Immunology, Biomedical Center, Ludwig-Maximilians-University Munich, Großhaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Musumeci
authors.affiliation: Max-Planck-Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany.|Department of Biology, University of Cologne, Zülpicher Str. 47, 50829 Cologne, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Failmezger
authors.affiliation: Institute for Immunology, Biomedical Center, Ludwig-Maximilians-University Munich, Großhaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Shu-Hung
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Max-Planck-Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany.|Department of Biology, University of Cologne, Zülpicher Str. 47, 50829 Cologne, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Tresch
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Timm
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Institute for Immunology, Biomedical Center, Ludwig-Maximilians-University Munich, Großhaderner Str. 9, 82152 Martinsried, Germany.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Krug
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005269:Femur / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics / Q000276:immunology; D059010:Single-Cell Analysis / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013977:Tibia / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C119309:CC chemokine receptor 9; D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D054388:Receptors, CCR; D063265:Sialic Acid Binding Immunoglobulin-like Lectins