Journal
CELL REPORTS
Volume 17, Issue 9, Pages 2445-2459Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.10.052
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Funding
- Ludwig Institute for Cancer Research
- MSKCC Center for Metastasis Research
- MSK Cancer Center from the National Cancer Institute [P30 CA008748]
- Gerstner Sloan Kettering Graduate School
- National Cancer Institute fellowship [5F31CA167863]
- Deutsche Forschungsgemeinschaft fellowships [KL 2491/1-1, SE2234/1-1]
- American Brain Tumor Association
- Canadian Institutes of Health Research
- [R01CA181355]
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Extensive transcriptional and ontogenetic diversity exists among normal tissue-resident macrophages, with unique transcriptional profiles endowing the cells with tissue-specific functions. However, it is unknown whether the origins of different macrophage populations affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone-marrow-derived macrophages (BMDMs) are present in tumors of the brain, a tissue with no homeostatic involvement of BMDMs. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing to demonstrate that BMDMs are abundant in primary and metastatic brain tumors. Our data indicate that distinct transcriptional networks in brain-resident microglia and recruited BMDMs are associated with tumor-mediated education yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between microglia and BMDMs in primary and metastatic disease in mouse and human.
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