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

Nora Hagemeyer, Katrin Kierdorf, Kathrin Frenzel, Jia Xue, Marc Ringelhan, Zeinab Abdullah, Isabelle Godin, Peter Wieghofer, Marta Joana Costa Jordão, Thomas Ulas, Gülden Yorgancioglu, Frank Rosenbauer, Percy A. Knolle, Mathias Heikenwalder, Joachim L. Schultze, Marco Prinz

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

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-kitCX3CR1+F4/80+ (A2) progenitors of the YS as the source of F4/80hi but not CD11bhi MΦ. Large-scale transcriptional profiling of MΦ precursors from the YS stage to adulthood allowed for building computational models for F4/80hi tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80hi and CD11bhi 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.

Original languageEnglish
Pages (from-to)1730-1744
Number of pages15
JournalEMBO Journal
Volume35
Issue number16
DOIs
StatePublished - 15 Aug 2016

Keywords

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

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