title: Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.
abstract: Recent studies have shown that tissue macrophages (MΦ) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MΦ can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate-mapping system that facilitated the identification of CD45(+)c-kit(-)CX3CR1(+)F4/80(+) (A2) progenitors of the YS as the source of F4/80(hi) but not CD11b(hi) MΦ. Large-scale transcriptional profiling of MΦ precursors from the YS stage to adulthood allowed for building computational models for F4/80(hi) tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80(hi) and CD11b(hi) MΦ and found that Irf8 was vital for MΦ maturation. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MΦ.
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Hagemeyer
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kierdorf
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Frenzel
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
authors.forename: Jia
authors.initials: J
authors.lastname: Xue
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz-Zentrum Munich, Munich, Germany Second Medical Department, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Ringelhan
authors.affiliation: Institute of Experimental Immunology, University Bonn, Bonn, Germany.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdullah
authors.affiliation: Gustave Roussy, INSERM U1170, Université Paris-Saclay, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Godin
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wieghofer
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Marta Joana
authors.initials: MJ
authors.lastname: Costa Jordão
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ulas
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
authors.forename: Gülden
authors.initials: G
authors.lastname: Yorgancioglu
authors.affiliation: Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenbauer
authors.affiliation: Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Institute of Virology, Technische Universität München/Helmholtz-Zentrum Munich, Munich, Germany Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: Institute of Neuropathology, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany marco.prinz@uniklinik-freiburg.de.
authors.forename: Marco
authors.identifier: 0000-0002-0349-1955
authors.initials: M
authors.lastname: Prinz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003198:Computer Simulation; D005260:Female; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D013234:Stem Cells / Q000502:physiology*; D015017:Yolk Sac / Q000166:cytology*; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8
keywords: CX3CR1; Kupffer cells; fate mapping; gene profiling; macrophages; microglia