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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 28, 2024 |
| Title |
Mediator Complex Subunit 1 Promotes Differentiation and Function of a Tumor-Specific T Regulatory Cell Population |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
T regulatory (Treg) cells engage specific transcriptional programs depending on the environmental and immunologic context. The Tregcell-intrinsic mechanisms differentially regulating these programs between tumors and other inflammatory settings remain to be determined. Here we show that Mediator complex subunit 1 (MED1) is required for Treg cell function specifically in the context of the tumor microenvironment. Treg cell-specific deletion of MED1 did not predispose mice to autoimmunity or affect Treg cell function in models of colitis, experimental autoimmune encephalomyelitis, or influenza infection. Surprisingly, mice with Treg cell-specific deletion of MED1 showed reduced growth in a wide range of tumors using both syngeneic and spontaneous cancer models. Single-cell RNA sequencing revealed that MED1 is required for the terminal differentiation of effector Treg cells in the tumor. Suppression of these terminally differentiated Treg cells, high in Tigit, Tnfrsf18, Tnfrsf9, Icos, and Ccr8, was sufficient for eliciting antitumor immunity. MED1 did not regulate chromatin accessibility or expression of effector transcription factors in intratumoral Treg cells but did promote transcription of genes involved in effector differentiation. Lastly, we found that both human and murine Treg cells experienced divergent paths of differentiation by comparing cells in tumors and matched tissues with non-malignant inflammation to demonstrate this subset's specificity to tumors. Collectively, we identified a novel pathway regulating the differentiation of a Treg cell effector subset specific to tumors and demonstrated that suppression of a subset of Treg cells is sufficient for promoting antitumor immunity in the absence of autoimmune consequences.
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| Overall design |
Treg cells were isolated from different tissues and subjected to sequencing.
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| Contributor(s) |
Chaudhuri S, Wang D, Weinberg SE, Fang D |
| Citation(s) |
38428427 |
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| Submission date |
Jul 21, 2023 |
| Last update date |
Apr 17, 2024 |
| Contact name |
Deyu Fang |
| E-mail(s) |
Fangd@northwestern.edu
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| Organization name |
Northwestern University
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| Street address |
303 E Chicago Avenue
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| City |
Chicago |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (3) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA997310 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237966_RAW.tar |
4.2 Gb |
(http)(custom) |
TAR (of BEDGRAPH, MTX, TDF, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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