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Published on: July 17, 2017
Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation
Nora Hagemeyer1, Katrin Kierdorf1, Kathrin Frenzel1
1Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
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.
Insights
Embryonic yolk sac progenitors give rise to specific tissue macrophages (MΦ). This study identifies their distinct transcriptional profiles and developmental pathways, revealing key molecular signatures for macrophage maturation.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Tissue macrophages (MΦ) originate from embryonic progenitors in the yolk sac (YS) and fetal liver, colonizing tissues prenatally.
- Distinct tissue MΦ populations have been proposed based on F4/80 and CD11b expression, but their unique transcriptional profiles remain largely uncharacterized.
Purpose of the Study:
- To identify the specific embryonic progenitors responsible for distinct tissue macrophage populations.
- To characterize the transcriptional profiles of developing tissue macrophages.
- To elucidate the molecular mechanisms governing macrophage maturation.
Main Methods:
- Utilized an inducible fate-mapping system to trace progenitor cells.
- Employed large-scale transcriptional profiling of macrophage precursors from embryonic to adult stages.
- Developed computational models to analyze lineage relationships.
Main Results:
- Identified CD45(+)c-kit(-)CX3CR1(+)F4/80(+) (A2) progenitors from the YS as the source of F4/80(hi) macrophages.
- Established that F4/80(hi) macrophages are direct descendants of A2 progenitors.
- Discovered distinct molecular signatures for F4/80(hi) and CD11b(hi) macrophages.
- Demonstrated the critical role of Irf8 in macrophage maturation.
Conclusions:
- YS-derived A2 progenitors are the exclusive source of F4/80(hi) tissue macrophages.
- Distinct transcriptional profiles differentiate embryonic-derived macrophage subsets.
- Irf8 is essential for the maturation of tissue macrophages, providing new insights into their development.
