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GSE43929
Mus musculus
4 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN- and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
Publication Title
Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background and aims: Dysregulation of intestinal epithelial cells performance associates with an array of pathologies whose onset mechanisms are incompletely understood. The aim of the present study was to provide a map of gene expresssion patterns along the human healthy adult gastro-intestinal tract and to implement a new procedure for microarray data noise filtering that would allow their use as a reference when screening for pathological deviations, such as inflammatory bowel disease (IBD). Methods: Gene expression profiles in antrum, duodenum, jejunum, ileum and transverse colon biopsies were measured with the Affymetrix U133A array and principal component analysis was used to identify region-selective biomarkers. These data were intersected with highly variable genes from a public dataset of gene expression in the ileal and colonic healthy regions of UC and Crohns disease patients. Moreover, gene sets covering gut functions not entirely accounted for by the available public tools were constructed to monitor their expression along the GI tract. Results: 166 genes were found to be responsible for distinguishing the five regions considered. Fourteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion, and six other novel genes. Similar analysis of the IBD datasets revealed that samples stratify based on disease rather than on the intestinal region. This withstanding, eleven genes were identified as possible early predictors of Crohns and/or UC in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. Conclusions: This novel approach, validated by retrieving known gene profiles, allowed the identification of promising new leads both in health and IBD state.
Publication Title
Biomarkers of human gastrointestinal tract regions.
Sample Metadata Fields
Age
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Global transcriptome patterns were performed using ORE1-IOE-2h (2h after Estradiol and Mock treatment) as well as transiently (6h) overexpressed Arabidopsis mesophyll cell protoplasts
Publication Title
NAC transcription factor ORE1 and senescence-induced BIFUNCTIONAL NUCLEASE1 (BFN1) constitute a regulatory cascade in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To determine the role of RPX on cell proliferation and organ development, we performed microarray experiments in search of RPX target genes by using an estradiol-inducible RPXC protein.
Publication Title
An upstream regulator of the 26S proteasome modulates organ size in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We profiled spinal cord tissue at the site of a moderate contusion injury at the level of the thoracic spinal cord
Publication Title
TrkB.T1 contributes to neuropathic pain after spinal cord injury through regulation of cell cycle pathways.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Drosophila melanogaster
- 36 Downloadable Samples
Ion Torrent Proton
Description
RNA expression was measured by RNA-seq in Drosophila ML-DmBG3-c2 cells depleted for proteins involved in sister chromatid cohesion, and in developing third instar wing discs with or withough brca2 gene mutations Overall design: RNA expression in depleted cells was compared to mock treated cells and RNA expression in wing discs from brca2 mutant Drosophila was compared to expression in wing discs without brca2 mutations This series includes mock RNAi treated samples re-used from GSE100547.
Publication Title
Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (Raidd) functions as a dual adaptor protein due to its bipartite nature, and is therefore thought to be a constituent of different multiprotein complexes including the PIDDosome, where it connects the cell death-related protease, Caspase-2, with the p53-induced protein with a death domain 1 (Pidd1). As such, Raidd has been implicated in DNA-damage-induced apoptosis as well as in tumor suppression, the latter based on its role as a direct activator of Caspase-2, known to delay lymphomagenesis caused by overexpression of c-Myc or loss of ATM kinase. As loss of Caspase-2 leads to an acceleration of tumor onset in the E-Myc mouse model we set out to interrogate the role of Raidd in this process in more detail. Our data obtained analyzing E-Myc/Raidd-/- mice indicate that Raidd is unable to protect from c-MYC-driven lymphomagenesis. Similarly, we failed to observe an effect of Raidd-deficiency on thymic lymphomagenesis induced by y-irradiation or fibrosarcoma development driven by 3-methylcholanthrene. The role of Caspase-2 as a tumor suppressor can therefore be uncoupled from its ability to interact and auto-activate upon binding to Raidd. Further, we provide supportive evidence that the tumor suppressive role of Caspase-2 is related to maintaining genomic integrity and allowing efficient p53-mediated signaling. Overall, our findings suggest that Raidd, although described to be the key-adapter allowing activation of the tumor suppressor Caspase-2, fails to suppress tumorigenesis in vivo.
Publication Title
The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold protein Raidd.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 14 Downloadable Samples
- Ion Torrent Proton
Description
RNA expression was measured using RNA-seq Overall design: RNA levels in Mock-treated control Drosophila cells were compared to RNA levels in cells RNAi depleted for Ph, Sce, and Pc
Publication Title
Polycomb repressive complex 1 modifies transcription of active genes.
Sample Metadata Fields
Subject
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Ion Torrent Proton
Description
RNA nascent transcription was measured using NT-seq Overall design: RNA nascent transcript levels in Mock-treated control Drosophila cells were compared to those in cells RNAi depleted for Ph and Sce
Publication Title
Polycomb repressive complex 1 modifies transcription of active genes.
Sample Metadata Fields
Subject
View Samples