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GSE54229
Mus musculus
13 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Therapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32C) or normothermia (37C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.
Publication Title
Estimating differential expression from multiple indicators.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1a treatment (Rebif, 22 g or 44 g three times a week) in patients with relapsing-remitting form of multiple sclerosis (MS). By using Affymetrix DNA microarrays, we obtained genome-wide expression profiles of peripheral blood mononuclear cells from 12 MS patients within the first two years of IFN-beta administration.
Publication Title
Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.
Publication Title
Smac mimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells for TNF-α-independent apoptosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gene expression is tightly linked to histone acetylation on lysine residues that can be recognized by bromodomains. The testis-specific bromodomain protein tBRD-1 is essential for male fertility and might act as a co-factor of testis-specifc TAFs. Here, we perform microarray analyses and demonstrate that tBRD-1 selectively controls gene expression in male germ cells
Publication Title
tBRD-1 selectively controls gene activity in the Drosophila testis and interacts with two new members of the bromodomain and extra-terminal (BET) family.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
IlluminaHiSeq2500
Description
The human nuclear poly(A)-binding protein PABPN1 has been implicated in the decay of nuclear noncoding RNAs (ncRNAs). In addition, PABPN1 stimulates hyperadenylation by poly(A) polymerase, and this activity is thought to be required for decay. Here, we inactivated hyperadenylation by two distinct mechanisms and examined changes in gene expression in HEK293 cells by RNAseq. We observed the upregulation of various ncRNAs, including snoRNA host genes, primary miRNA transcripts, and upstream antisense RNAs, confirming that hyperadenylation is broadly required for the degradation of PABPN1-targets. In addition, we found that mRNAs with retained introns are susceptible to PABPN1 and PAPa/?-mediated decay (PPD). Transcripts are targeted for degradation due to inefficient export, which is a consequence of reduced intron number or incomplete splicing. We conclude that PPD is an important mammalian nuclear RNA decay pathway for the removal of poorly spliced and nuclear-retained transcripts. Overall design: Poly(A)+ RNA from HEK293 cells was analyzed by next generation sequencing following depletion of PAPa and PAP? or expression of a dominant negative allele of PABPN1 (LALA) designed to inhibit polyadenylation. For each condition, we collected both total RNA and a nuclear-enriched sample. Each sample was collected in duplicate.
Publication Title
Canonical Poly(A) Polymerase Activity Promotes the Decay of a Wide Variety of Mammalian Nuclear RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Complex three-dimensional (3D) in vitro model systems that recapitulate human tumor biology are essential to better understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellula communication, nutrient and oxygen gradients, and cell polarity that is lacking in traditional two-dimensional (2D) monolayer cultures. In the present study, we could demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of Erb family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we could provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.
Publication Title
Organotypic three-dimensional cancer cell cultures mirror drug responses <i>in vivo</i>: lessons learned from the inhibition of EGFR signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Acute myeloid leukemia (AML), and other myeloid malignancies, are frequently treated with hypomethylating agents like decitabine. Alterations in the epigenome, induced by decitabine, are likely to result in gene expression changes. The effects of decitabine have not been systemically studied using primary AML samples.
Publication Title
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina Genome Analyzer II, Illumina HiSeq 2000
Description
Purpose: The purpose of this experiment is to expand the repertoire of C. elegans edited transcripts and identify the roles of ADR-1 as indirect regulator of editing and ADR-2 as the only active deaminase in vivo. Methods: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline. Results: Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3’ UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2; and mutations within its dsRNA binding domains abolished both binding and editing regulation. Conclusions: ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo and raises the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing by deaminase-independent mechanisms. Overall design: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline.
Publication Title
The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and Programmed death-1 (PD-1) are immunoregulatory receptors expressed on T cells that play important roles in suppressing immune responses to cancer. Although monoclonal antibodies that target CTLA-4 or PD-1 stimulate therapeutic anti-tumour T cell responses, the tumour antigens recognized by checkpoint blockade immunotherapy remain undefined. Herein, we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T cell rejection antigens following aPD-1 and/or aCTLA-4 treatment of mice bearing progressively growing sarcomas. We validate this conclusion by showing that (a) the predicted mutant epitopes associate with MHC class I molecules of the tumour; (b) T cells specific for these mutant epitopes infiltrate tumours; and (c) therapeutic vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Whereas, T cells with the same antigen specificity are present in progressively growing tumours in control mice, tumour-specific T cells in aPD-1- and/or aCTLA-4-treated mice express some overlapping but mostly treatment-specific transcriptional profiles that render them capable of tumour rejection. Thus, tumour-specific mutant antigens are not only important targets of checkpoint blockade therapy but also can be used to identify tumour antigen-specific T cells that function as biomarkers of successful anti-tumour responses. Overall design: For sorting of mLama4-specific cells, tumour-infiltrating cells were enriched for CD45+ cells using CD45 cell purification magnetic beads (Miltenyi Biotec). CD45 enriched cells were then sorted gating for PI- CD3e+ CD8a+ mLama4-tetramer-PE+ or PI- CD3e+ CD8a+ mLama4-tetramer-PE- cells. Sorting was performed on a BD FACSAria II (BD Biosciences). Sorted cells were pelleted and processed for RNA analysis. All flow cytometry was performed on the FACSCalibur (BD Biosciences) or LSR Fortessa (BD Biosciences) and analysed using FlowJo software (TreeStar).
Publication Title
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens.
Sample Metadata Fields
No sample metadata fields
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