|
| Status |
Public on Sep 07, 2016 |
| Title |
A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells (batch 1) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact.
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| |
|
| Overall design |
CD8 TILs from WT and MTKO mice were sequenced at single-cell resolution
|
| |
|
| Contributor(s) |
Singer M |
| Citation(s) |
27610572 |
| |
| Submission date |
Aug 24, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Meromit Singer |
| E-mail(s) |
msinger@broadinstitute.org
|
| Organization name |
Broad Institute of MIT and Harvard
|
| Street address |
415 main st, ROOM 6031
|
| City |
CAMBRIDGE |
| State/province |
MASSACHUSETTS |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (384)
|
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| This SubSeries is part of SuperSeries: |
| GSE86042 |
A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells |
|
| Relations |
| BioProject |
PRJNA340022 |
| SRA |
SRP082755 |
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