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GSE73001
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Publication Title
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Publication Title
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2000, IlluminaGenomeAnalyzerIIx
Description
Type 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo. Overall design: There are three experiments in this submission. All are in human islets or islet cell types. The first is a comparison of miRNA levels in sorted alpha versus beta cells. There is one replicate for this experiment. The second experiment is to measure the expression of miRNAs in whole islets as a function of glucose levels. There are three levels and one replicate for each condition. The third exeriment is a comparison of whole islets taken from human donors that were suspected/confirmed Type 2 diabetic or considered controls. There are 3 controls and 4 T2D samples.
Publication Title
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing ß-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human ß-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased ß-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM. Overall design: Identification of miRNA-target interaction in human islets using HITS-CLIP, one mRNA library and one miRNA library
Publication Title
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed RNA sequencing to assess changes in gene expression in lung cancer cell lines with MET genetic alterations with or without co-occurrence of JAK2 inactivating mutations. Different treatments have been administrated to activate or inhibit selected pathways in order to define MET signature and IFNg (or JAK/STAT) signature. Overall design: Differential expression analysis of RNA sequencing of 4 different lung cancer cell lines with MET genetic alterations treated with different treatements to activate or inhibit selected pathways
Publication Title
<i>MET</i>-Oncogenic and <i>JAK2</i>-Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We investigated the impact of on miR-H1 and miR-K12-3-3p- on host transcriptome focusing on gingival epithelial cells that are target sites for various HHV.
Publication Title
Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells).
Publication Title
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Here, we examined the host response relative of SACC-PHHs infected with either hepatitis B virus (HBV) alone or both HBV/hepatitis delta virus (HDV) co-infection compared to non-infected controls. Overall design: SACC-PHHs were generated with PHHs from either a single human donor or mixed donors (in total, there were five donors) and co-cultured with 3T3J mouse non-parenchymal cells. These cultures can be persistently infected for up to 1-1.5 months post-challenge and exhibit a transcriptomic profile similar to what's observed in the 3D context of the liver. Note that not all donors and conditions have the same number of replicates.
Publication Title
Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here we present evidence that prostate cancer stem-like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSC were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T cell receptor-dependent T cell activation, proliferation and cytokine production. Mechanistically, TNC interacted with 51 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system.
Publication Title
Tenascin-C Protects Cancer Stem-like Cells from Immune Surveillance by Arresting T-cell Activation.
Sample Metadata Fields
Specimen part
View Samples