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| Status |
Public on May 05, 2022 |
| Title |
Tumor-associated macrophage functional heterogeneity is driven by niche diversity in breast cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The concept of macrophage niches has redefined the classification of macrophages, moving beyond ontogeny and function to encompass the mutually beneficial loop of signals in a given tissue environment. As such, tissue-resident macrophages adapt to local environmental signals within and between tissues to acquire specific functional adaptations. Neoplastic transition transforms the tissue environment, which then raises the question as to how existing macrophage subsets and their niche contribute to the tumor-associated macrophage (TAM) compartment. By combining single cell RNA sequencing and 2-photon imaging, we discovered that considerable TAM heterogeneity in mammary breast tumor is driven by niches that exist prior to tumor development, macrophage localization within the tumor and the stage of tumor malignancy. The differentiation of TAM subsets was associated with distinct signaling paths, homing and transcription factor signatures. We find similar functional heterogeneity in human breast TAMs. In overview, we show that specific niches within the tumor rather than defined activation states (e.g. the M1/M2 dichotomy) are the major drivers of TAM plasticity and heterogeneity. The distinctions created by this analysis show how treatments of different tumor indications should propose targeting specific TAMs at this niche/pathway level.
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| Overall design |
3 sorted tumor samples from a pool of 4 mice(spontaneous tumors; bulk myeloid, cd11b-hi-enriched, and cd11b-lo-enriched) 1 sorted tumor samples from a pool of 5 mice(orthotopically injected tumors; bulk myeloid)
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| Contributor(s) |
Laviron M, Petit M, Weber-Delacroix E, Combes AJ, Rao AA, Barthélémy S, Courau T, Hume DA, Combadière C, Krummel MF, Boissonnas A |
| Citation(s) |
35613577 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| U01 CA217864 |
Integrating targeted and immunotherapy to treat genetically heterogeneous cancers |
University of California San Francisco |
MATTHEW F KRUMMEL |
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| Submission date |
Sep 14, 2021 |
| Last update date |
Aug 16, 2022 |
| Contact name |
Arjun Arkal Rao |
| E-mail(s) |
arjunarkal.rao@ucsf.edu
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| Organization name |
University of California, San Francisco
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| Department |
CoLabs
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| Lab |
Data Sciences CoLab
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| Street address |
505 Parnassus Ave, S-447
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA763178 |
| SRA |
SRP337024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE184096_RAW.tar |
152.3 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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