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Transcriptome‐based profiling of yolk sac‐derived macrophages reveals a role for Irf8 in macrophage maturation
Author(s) -
Hagemeyer Nora,
Kierdorf Katrin,
Frenzel Kathrin,
Xue Jia,
Ringelhan Marc,
Abdullah Zeinab,
Godin Isabelle,
Wieghofer Peter,
Costa Jordão Marta Joana,
Ulas Thomas,
Yorgancioglu Gülden,
Rosenbauer Frank,
Knolle Percy A,
Heikenwalder Mathias,
Schultze Joachim L,
Prinz Marco
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201693801
Subject(s) - biology , transcriptome , profiling (computer programming) , irf8 , microbiology and biotechnology , gene expression profiling , yolk sac , macrophage , cd163 , immunology , genetics , transcription factor , phenotype , gene expression , gene , embryo , computer science , in vitro , operating system
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 CD 11b, 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 CD 45 + c‐kit − CX 3 CR 1 + F4/80 + (A2) progenitors of the YS as the source of F4/80 hi but not CD 11b 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 CD 11b 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.