The presence of the PTPN22 risk variant (1858T) is associated to several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk variant on T cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve CD4+ T cells carrying two PTPN22 risk alleles overexpress a limited number of genes including CFLAR and 4-1BB important for cytotoxic T cell differentiation. Moreover, an increased number of cytotoxic EOMES+ CD4+ T cells were observed in PTPN22 risk allele carriers, which negatively correlated with a decreased number of naïve T cells in older individuals. No difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg) was observed in PTPN22 risk allele carriers and Treg suppressive capacity was not altered. Finally, in synovial fluids of RA patients, an accumulation of EOMES+ CD4+ T cells was observed with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, our data provide a novel mechanism of action of PTPN22 risk variant on CD4+ T-cell differentiation and identify EOMES+ CD4+ T cell as a relevant T cell subset in RA. Overall design: Healthy blood donors were selected based PTPN22 genotype, and RNA-sequencing was done on CD4 T cells
EOMES-positive CD4<sup>+</sup> T cells are increased in PTPN22 (1858T) risk allele carriers.
Sex, Age, Subject
View SamplesFibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.
Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Age
View SamplesWe report transcriptome of nascent teratoma cell-derived pluripotent stem cells, Dnd1-KD ESCs and control ESC by RNA-seq. Overall design: RNA-seq of two independent pluripotent stem cell lines derived form nascent teratoma cell in new-born testis of Dnd1-deficient mice, control E14tg2a ESCs and Dnd1-KD ESCs in dupulicate by using Illumina HiSeq2500.
Derivation of pluripotent stem cells from nascent undifferentiated teratoma.
Disease, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.
Sex, Age
View SamplesThis study was conducted in order to identify biomarkers for a prognostic gene expression signature for metastases in early stage CRC.
A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.
Sex, Age
View SamplesLocated in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all other liver cell types by physical association and / or by producing cytokines and chemokines. In liver disease and folllowing liver transplantation, elevated levels of endotoxin (bacterial lipopolysaccharide: LPS) stimulate HSCs to produce increased amounts of cytokines and chemokines. Transcriptomic analysis of cultured HSCs stimulated with LPS yields a survey of expression changes which potentially modulate the hepatic inflammatory and immune responses.
The transcriptomic response of rat hepatic stellate cells to endotoxin: implications for hepatic inflammation and immune regulation.
Sex, Specimen part
View SamplesThis analysis identified 27 genes that are induced, and 29 that are repressed, by a factor of two or more in Asr1RING mutant cells. Genes in each category did not cluster according to gene ontology or chromosome, but we did notice that 33% of genes in the induced set lie within 50 kb of a telomere. In contrast, for repressed genes, only 7% were similarly telomere-proximal. The induction of subtelomeric gene expression in Asr1RING mutant cells suggests that the Ub-ligase activity of Asr1 may be required for authentic patterns of subtelomeric gene silencing. Overall design: Transcriptome of WT and Asr1 RING mutant cells grown at log phase in enriched media.
Antagonistic roles for the ubiquitin ligase Asr1 and the ubiquitin-specific protease Ubp3 in subtelomeric gene silencing.
Subject
View SamplesTumors of advanced gastric cancer patients were biopsied and subjected to gene expression profiling using the Affymetrix Human Genome U133 Plus 2.0 Arrays. Patients were then segregated into G1, G2 or G3 groups based on their tumor genomic profiles. Patients in the G1 and G3 cohorts were assigned SOX (oxaliplatin plus S-1) chemotherapy whereas those in the G2 cohort were given SP (cisplatin plus S-1) regimen.
Real-Time Tumor Gene Expression Profiling to Direct Gastric Cancer Chemotherapy: Proof-of-Concept "3G" Trial.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis.
Disease stage
View SamplesCell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation
ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis.
Disease stage
View Samples