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Series GSE86028 Query DataSets for GSE86028
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.
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
Organization name Broad Institute of MIT and Harvard
Street address 415 main st, ROOM 6031
State/province MASSACHUSETTS
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (384)
GSM2290796 AH3VMFBGXY_A10_S106
GSM2290797 AH3VMFBGXY_A10_S10
GSM2290798 AH3VMFBGXY_A10_S202
This SubSeries is part of SuperSeries:
GSE86042 A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells
BioProject PRJNA340022
SRA SRP082755

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE86028_TILs_sc_wt_mtko.index.txt.gz 6.3 Kb (ftp)(http) TXT
GSE86028_TILs_sc_wt_mtko.tpm.log2.txt.gz 11.5 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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