Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies Academic Article uri icon

Overview

MeSH Major

  • Brain Neoplasms
  • DNA Transposable Elements
  • Glioma

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.

publication date

  • November 22, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5450644

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.10.052

PubMed ID

  • 27840052

Additional Document Info

start page

  • 2445

end page

  • 2459

volume

  • 17

number

  • 9