PMID- 27840052 OWN - NLM STAT- MEDLINE DCOM- 20171121 LR - 20181113 IS - 2211-1247 (Electronic) VI - 17 IP - 9 DP - 2016 Nov 22 TI - Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies. PG - 2445-2459 LID - S2211-1247(16)31472-3 [pii] LID - 10.1016/j.celrep.2016.10.052 [doi] AB - 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. CI - Copyright A(c) 2016 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Bowman, Robert L AU - Bowman RL AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Sloan Kettering Graduate School of Biomedical Science, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Klemm, Florian AU - Klemm F AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Oncology, University of Lausanne, 1066 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1066 Lausanne, Switzerland. FAU - Akkari, Leila AU - Akkari L AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Oncology, University of Lausanne, 1066 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1066 Lausanne, Switzerland. FAU - Pyonteck, Stephanie M AU - Pyonteck SM AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Sevenich, Lisa AU - Sevenich L AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Quail, Daniela F AU - Quail DF AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Dhara, Surajit AU - Dhara S AD - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Simpson, Kenishana AU - Simpson K AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Gardner, Eric E AU - Gardner EE AD - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Iacobuzio-Donahue, Christine A AU - Iacobuzio-Donahue CA AD - Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Brennan, Cameron W AU - Brennan CW AD - Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Tabar, Viviane AU - Tabar V AD - Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Gutin, Philip H AU - Gutin PH AD - Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. FAU - Joyce, Johanna A AU - Joyce JA AD - Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Oncology, University of Lausanne, 1066 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1066 Lausanne, Switzerland. Electronic address: johanna@joycelab.org. LA - eng GR - F31 CA167863/CA/NCI NIH HHS/United States GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R01 CA181355/CA/NCI NIH HHS/United States GR - CIHR/Canada PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20161110 PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 RN - 0 (Transcription Factors) RN - 143198-26-9 (Integrin alpha4) SB - IM MH - Animals MH - Base Sequence MH - Bone Marrow Cells/pathology MH - Brain Neoplasms/genetics/*pathology MH - Cell Lineage MH - Disease Models, Animal MH - Gene Expression Regulation, Neoplastic MH - Gene Regulatory Networks MH - Glioma/genetics/pathology MH - Humans MH - Integrin alpha4/metabolism MH - Macrophage Activation MH - Macrophages/metabolism/*pathology MH - Mice MH - Microglia/metabolism/pathology MH - Sequence Analysis, RNA MH - Transcription Factors/metabolism PMC - PMC5450644 MID - NIHMS858933 OTO - NOTNLM OT - CD49D OT - Macrophage OT - brain metastasis OT - glioma OT - microglia OT - tumor-associated macrophages EDAT- 2016/11/15 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/05/31 CRDT- 2016/11/15 06:00 PHST- 2016/09/18 00:00 [received] PHST- 2016/10/12 00:00 [revised] PHST- 2016/10/19 00:00 [accepted] PHST- 2016/11/15 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2016/11/15 06:00 [entrez] PHST- 2017/05/31 00:00 [pmc-release] AID - S2211-1247(16)31472-3 [pii] AID - 10.1016/j.celrep.2016.10.052 [doi] PST - ppublish SO - Cell Rep. 2016 Nov 22;17(9):2445-2459. doi: 10.1016/j.celrep.2016.10.052. Epub 2016 Nov 10.