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EMBO J. 2016 Aug 15;35(16):1730-44. doi: 10.15252/embj.201693801. Epub 2016 Jul 13.

Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.

Author information

1
Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
2
Genomics and Immunoregulation, LIMES-Institute, University of Bonn, Bonn, Germany.
3
Institute of Virology, Technische Universität München/Helmholtz-Zentrum Munich, Munich, Germany Second Medical Department, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
4
Institute of Experimental Immunology, University Bonn, Bonn, Germany.
5
Gustave Roussy, INSERM U1170, Université Paris-Saclay, Villejuif, France.
6
Institute of Molecular Tumor Biology, University of Muenster, Muenster, Germany.
7
Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
8
Institute of Virology, Technische Universität München/Helmholtz-Zentrum Munich, Munich, Germany Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
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.
10
Institute of Neuropathology, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany marco.prinz@uniklinik-freiburg.de.

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.

KEYWORDS:

CX3CR1; Kupffer cells; fate mapping; gene profiling; macrophages; microglia

PMID:
27412700
PMCID:
PMC5010043
DOI:
10.15252/embj.201693801
[Indexed for MEDLINE]
Free PMC Article

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