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| Status |
Public on Jun 09, 2023 |
| Title |
MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The histone variant macroH2A has been implicated as a tumor suppressor in melanoma and other cancers, yet its role in the tumor microenvironment remains unappreciated. Here we show that mice constitutively lacking macroH2A variants exhibit increased melanoma tumor burden compared to their wild-type counterparts, which is associated with an altered intratumoral immune cell compartment. MacroH2A-deficient tumors display an accumulation of immunosuppressive monocytes and decreased functional cytotoxic T cells. Consistent with this compromised anti-tumor response, macroH2A-deficient tumors displayed upregulation of chemokines such as Ccl2, Cxcl1 and Il6. Through single cell transcriptomics of the entire melanoma microenvironment, we identified the source of these pro-tumor myeloid chemoattractants as cancer-associated fibroblasts, whose frequency and activation were increased in the absence of macroH2A. Chemokine gene expression was hyper-inducible in the absence of macroH2A and accompanied by an altered epigenetic landscape. In sum, we uncovered a tumor suppressive role for macroH2A through repression of chemokine induction in the tumor stroma.
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| Overall design |
Single cell profiling of gene expression was carried out in WT and macroH2A deficient melanomas was carried out to identify cell types involved in increased tumor growth and chemokine overexpression in the absence of macroH2A.
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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
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| Phone |
2128249265
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Oncological Sciences
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| Lab |
Emily Bernstein
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| Street address |
1470 Madison Ave
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE200751 |
MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts. |
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| Relations |
| BioProject |
PRJNA954845 |
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