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Series GSE200734 Query DataSets for GSE200734
Status Public on Jun 09, 2023
Title MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts [epigenomics]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
Overall design Epigenomic analysis of sorted or cultured CAFs from WT and macroH2A melanomas was carried out to understand how macroH2A regulates inflammatory gene expression in this cell type. iDFs were used as a related cell type, developed individually, to validate these findings.
Contributor(s) Filipescu D, Bernstein E
Citation(s) 37605008
Submission date Apr 13, 2022
Last update date Sep 20, 2023
Contact name Dan Filipescu
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 (13)
GSM6042890 Mouse # 66620 CAF ATAC-seq
GSM6042891 Mouse # 66626 CAF ATAC-seq
GSM6042892 Mouse # 66623 CAF ATAC-seq
This SubSeries is part of SuperSeries:
GSE200751 MacroH2A restricts melanoma progression via inhibition of chemokine expression in cancer-associated fibroblasts.
BioProject PRJNA826452

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Supplementary file Size Download File type/resource
GSE200734_RAW.tar 1.9 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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