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Series GSE140431 Query DataSets for GSE140431
Status Public on Dec 03, 2019
Title IL-33 signaling alters regulatory T cell diversity in support of tumor development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single cell RNA-Seq to longitudinally profile dynamic shifts in the distribution of Tregs in a genetically-engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive Tregs are more prevalent early in tumor development, while a specialized effector phenotype characterized by enhanced expression of the interleukin 33 receptor ST2 is predominant in advanced disease. Treg-specific deletion of ST2 alters the evolution of effector Treg diversity, increases infiltration of CD8+ T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention.
Overall design Tumors were microdissected and dissociated into single cell suspensions. CD45+ and CD45- cells were then magnetically separated using MACS CD45 MicroBeads (Miltenyi Biotec) as per manufacturer’s instructions. CD45+ and CD45- single cells were processed through the 10X Genomics Single Cell 3' platform using the Chromium Single Cell 3′ Library & Gel Bead Kit V2 kit (10X Genomics), per manufacturer’s protocol. Briefly, 6,000 cells were loaded onto each channel. Cell lysis and barcoding occur, followed by amplification, fragmentation, adaptor ligation and index library PCR. Libraries were sequenced on an Illumina HiSeqX at a read length of 98 base pairs. De-multiplexing, alignment to the mm10 transcriptome and unique molecular identifier (UMI)-collapsing were performed using the Cellranger toolkit from 10X Genomics version 1.1.0.
Please note that the counts data is from both samples together, and the cell name entails both the cell barcode and also which sample this cell came from. 
Contributor(s) Li A, Herbst RH, Canner D, Schenkel JM, Smith OC, Kim JY, Hillman M, Bhutkar A, Cuoco MS, Rappazzo CG, Rogers P, Dang C, Jerby-Arnon L, Rozenblatt-Rosen O, Cong L, Birnbaum M, Regev A, Jacks T
Citation(s) 31801068
Submission date Nov 14, 2019
Last update date Dec 09, 2019
Contact name Rebecca H Herbst
Organization name Broad Institute of MIT and Harvard
Department Klarman Cell Observatory
Lab Aviv Regev
Street address 415 Main Street
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (2)
GSM4161233 Mouse lung adenocarcinoma scRNA-seq [O_45N]
GSM4161234 Mouse lung adenocarcinoma scRNA-seq [O_45P]
This SubSeries is part of SuperSeries:
GSE139232 IL-33 signaling alters regulatory T cell diversity in support of tumor development
BioProject PRJNA589674
SRA SRP229997

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

Supplementary file Size Download File type/resource
GSE140431_Cell_meta_info.txt.gz 174.8 Kb (ftp)(http) TXT
GSE140431_counts.txt.gz 28.7 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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