Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies Journal Article


Authors: Bowman, R. L.; Klemm, F.; Akkari, L.; Pyonteck, S. M.; Sevenich, L.; Quail, D. F.; Dhara, S.; Simpson, K.; Gardner, E. E.; Iacobuzio-Donahue, C. A.; Brennan, C. W.; Tabar, V.; Gutin, P. H.; Joyce, J. A.
Article Title: Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies
Abstract: 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. © 2016 The Authors
Keywords: glioma; brain metastasis; macrophage; microglia; tumor-associated macrophages; cd49d
Journal Title: Cell Reports
Volume: 17
Issue: 9
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2016-11-22
Start Page: 2445
End Page: 2459
Language: English
DOI: 10.1016/j.celrep.2016.10.052
PROVIDER: scopus
PUBMED: 27840052
PMCID: PMC5450644
DOI/URL:
Notes: Article -- Export Date: 3 January 2017 -- Source: Scopus
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MSK Authors
  1. Viviane S Tabar
    225 Tabar
  2. Philip H Gutin
    163 Gutin
  3. Cameron Brennan
    226 Brennan
  4. Johanna A Joyce
    67 Joyce
  5. Leila Akkari
    15 Akkari
  6. Robert L Bowman
    52 Bowman
  7. Stephanie Harris
    4 Harris
  8. Daniela Francis Quail
    13 Quail
  9. Eric Edison Gardner
    14 Gardner
  10. Florian   Klemm
    3 Klemm
  11. Surajit   Dhara
    2 Dhara