Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies
| Autor: | Lisa Sevenich, Stephanie M. Pyonteck, Surajit Dhara, Leila Akkari, Florian Klemm, Kenishana Simpson, Viviane Tabar, Daniela F. Quail, Johanna A. Joyce, Christine A. Iacobuzio-Donahue, Cameron Brennan, Eric E. Gardner, Robert L. Bowman, Philip H. Gutin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Macrophage Integrin alpha4 Gene regulatory network Bone Marrow Cells Tumor initiation 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 brain metastasis glioma microglia tumor-associated macrophages Biology CD49d General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Glioma medicine Transcription factor Microglia Brain Neoplasms Macrophages medicine.disease Chromatin 030104 developmental biology medicine.anatomical_structure Immunology Cancer research Transcription Factors |
| Zdroj: | Cell reports, vol. 17, no. 9, pp. 2445-2459 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.10.052 |
| Popis: | SummaryExtensive 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. |
| Databáze: | OpenAIRE |
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