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| Status |
Public on May 15, 2023 |
| Title |
Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tumor microenvironment components, including T and myeloid cells, play important roles in lung adenocarcinoma (LADC) progression and response to therapy. Here, we identify a role for Siah1a/2 ubiquitin ligases in controlling alveolar macrophage (AM) differentiation and urethane-induced LADC. Genetic ablation of Siah1a/2 in AMs enriched their immature state, coinciding with increased pro-tumorigenic and inflammatory gene signatures and abundance of Siah1a/2 substrates NRF2 and B-catenin. Urethane administration to mice enriched the population of monocytic and immature-like AMs, which were more prevalent in the lungs of mice carrying Siah1a/2-ablated macrophages. While resembling transitional profibrotic macrophages often seen in lung fibrosis, enrichment of immature AMs coincided with the development of more frequent and larger lung tumors in urethane-treated mice harboring Siah1a/2 ablated macrophages compared with controls. Gene expression signature of Siah1a/2 ablated immature-like AMs is associated with increased infiltration of CD14+ immune cells and worse survival of LADC patients. Our findings identify Siah1a/2 as gatekeepers of cancer development by controlling AM differentiation and profibrotic phenotypes contributing to carcinogen-induced lung cancer.
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| Overall design |
Cd45+ cells from WT and Siah1a/2 mutant mouse lungs were sorted using flow cytometry and gene expression analyzed using 10X Genomic scRNA-seq protocol.
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| Contributor(s) |
Scortegagna M, Ronai ZA |
| Citation(s) |
37078793 |
| |
| Submission date |
Oct 18, 2022 |
| Last update date |
Aug 14, 2023 |
| Contact name |
Ze'ev A. Ronai |
| E-mail(s) |
ronai@sbpdiscovery.org
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| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
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| Department |
Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center
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| Street address |
10901 North Torrey Pines Road
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE215993 |
Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma |
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| Relations |
| BioProject |
PRJNA891679 |
