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| Status |
Public on Jun 09, 2023 |
| Title |
MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts [3D chromatin] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
MacroH2A has tumor suppressive functions in melanoma and other cancers, yet its role in the tumor microenvironment remains unappreciated. Using an autochthonous, immunocompetent mouse model of melanoma, we demonstrate that mice devoid of macroH2A variants exhibit increased tumor burden compared to wild type counterparts. MacroH2A-deficient tumors accumulate immunosuppressive monocytes and decreased functional cytotoxic T cells, and consistent with this compromised anti-tumor response, exhibit upregulation of pro-inflammatory cytokines. Single cell transcriptomics not only identifies cancer-associated fibroblasts (CAFs), whose frequency and activation increase in the absence of macroH2A, as the source of myeloid chemoattractants but also demonstrates dedifferentiation along the neural crest lineage of the tumor compartment. CAFs lacking macroH2A display hyper-inducible inflammatory gene expression and promoters of these genes present increased chromatin looping to enhancers that gain H3K27ac. In sum, we reveal a tumor suppressive role for macroH2A variants through regulation of chromatin architecture of inflammatory genes in the tumor stroma with potential implications for human melanoma.
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| Overall design |
3D chromatin conformation analysis by Micro-C followed by promoter capture (pcMicro-C), in 2 replicates each in WT and dKO cultured CAFs
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| |
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| Contributor(s) |
Filipescu D, Bernstein E |
| Citation(s) |
37605008 |
| |
| Submission date |
Apr 12, 2023 |
| Last update date |
Sep 20, 2023 |
| Contact name |
Dan Filipescu |
| E-mail(s) |
dan.filipescu@mssm.edu
|
| Phone |
2128249265
|
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Oncological Sciences
|
| Lab |
Emily Bernstein
|
| Street address |
1470 Madison Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (4)
|
| GSM7164982 |
CAF culture from mouse # 66391 pcMicro-C replicate 1 |
| GSM7164983 |
CAF culture from mouse # 66391 pcMicro-C replicate 2 |
| GSM7164984 |
CAF culture from mouse # 66383 pcMicro-C replicate 1 |
| GSM7164985 |
CAF culture from mouse # 66383 pcMicro-C replicate 2 |
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| This SubSeries is part of SuperSeries: |
| GSE200751 |
MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts. |
|
| Relations |
| BioProject |
PRJNA954844 |
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