Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.

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Serval ID
serval:BIB_D0474EC65CDA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.
Journal
Cell reports
Author(s)
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.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
22/11/2016
Peer-reviewed
Oui
Volume
17
Number
9
Pages
2445-2459
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Animals, Base Sequence, Bone Marrow Cells/pathology, Brain Neoplasms/genetics, Brain Neoplasms/pathology, Cell Lineage, Disease Models, Animal, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Glioma/genetics, Glioma/pathology, Humans, Integrin alpha4/metabolism, Macrophage Activation, Macrophages/metabolism, Macrophages/pathology, Mice, Microglia/metabolism, Microglia/pathology, Sequence Analysis, RNA, Transcription Factors/metabolism, CD49D, Macrophage, brain metastasis, glioma, microglia, tumor-associated macrophages
Pubmed
Web of science
Open Access
Yes
Create date
05/12/2016 19:28
Last modification date
07/04/2021 6:34
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