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Series GSE86030 Query DataSets for GSE86030
Status Public on Sep 07, 2016
Title A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells (batch 3)
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
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)
GSM2291192 HYGHVBGXX_A10_S106
GSM2291193 HYGHVBGXX_A10_S10
GSM2291194 HYGHVBGXX_A10_S202
This SubSeries is part of SuperSeries:
GSE86042 A distinct gene module uncouples dysfunction from activation in tumor-infiltrating T cells
Relations
BioProject PRJNA340023
SRA SRP082756

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE86030_TILs_sc_wt_mtko.index.txt.gz 6.3 Kb (ftp)(http) TXT
GSE86030_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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