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| Status |
Public on Nov 10, 2016 |
| Title |
Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Recent efforts have uncovered immense transcriptional and ontogenetic diversity among tissue-resident macrophages, each with their own transcriptional profile endowing the cell with its tissue-specific functions. However, it is currently unknown whether the origins of different macrophage populations may affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone marrow-derived macrophages (BMDM) are even present in tumors of the brain, a tissue where there is no homeostatic involvement of peripherally-derived myeloid cells. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing models to demonstrate that BMDM are indeed abundant in primary and metastatic brain tumors. Transcriptional profiling of tumor-associated BMDM and resident microglia showed that these cells acquire substantially different gene expression profiles. Our data suggest that transcriptional networks in each cell population 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 brain-resident microglia and peripherally-derived macrophages in both primary and metastatic disease in mouse and human.
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| Overall design |
Tumor associated microglia and macrophages were isolated from mouse glioma tumors. Samples are provided as matched microglia and macrophages from 3 tumors.
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| |
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| Contributor(s) |
Bowman RL, Joyce JA |
| Citation(s) |
27840052 |
| |
| Submission date |
Sep 08, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Robert L Bowman |
| E-mail(s) |
bowmanr@mskcc.org
|
| Phone |
6468882059
|
| Organization name |
MSKCC
|
| Department |
HOPP
|
| Lab |
Levine Lab
|
| Street address |
430 East 67th Street
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (20)
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| Relations |
| BioProject |
PRJNA345301 |
| SRA |
SRP090798 |
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