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 F4/80hi 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.
In vivo fate mapping combined with transcriptomics shows the existence of different mouse macrophage subsets, and an important role for the transcription factor Irf8 in regulating their development.
Two distinct macrophage subsets are characterized by differential expression of F4/80 and CD11b.
F4/80hi but not CD11bhi macrophages originate from the yolk sac.
Distinct gene profile of F4/80hi and CD11bhi macrophages from embryogenesis until adulthood.
Irf8 is expressed in F4/80hi and CD11bhi macrophages during ontogeny.
Irf8 regulates tissue macrophage maturation.
The EMBO Journal (2016) 35: 1730–1744
- Received January 4, 2016.
- Revision received June 13, 2016.
- Accepted June 15, 2016.
- © 2016 The Authors
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