Filters
Technology
Platform
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Background. T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non obese diabetic (NOD) mouse strain. Results. Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data we identify differentially expressed candidate genes including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusions. The data provide a molecular map of the negative selection response in vivo, and by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.
Publication Title
Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
The left kidneys of 8 Sprague-Dawley rats were removed and the rats were left for 2 weeks to recover. After 4 additional days (during which blood pressure measurements were obtained), they were injected daily subcut. with either saline (1ml/kg), adrenocorticotropic hormone (ACTH, 0.2mg/kg) or dexamethasone (DEX, 0.02mg/kg) for 8 days before the right kidney was removed. ACTH and DEX treatment caused hypertension in the rats as illustrated by increased systolic blood pressure. The gene expression patterns of the kidneys were analysed using Affymetrix arrays.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples
GSE9700- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b)
Description
Microarray analysis of thymic deletion in the B10 mouse strain
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
Expression microarrays were employed to identify genes induced by phorbol ester and ionomycin stimulation of EL4 cells. EL4 is a murine T cell line. To identify induced genes that were independent of new protein synthesis cells were pre-treated with cycloheximide. This expression study was used in conjunction with histone acetylation ChIP-chip to determine if inducible genes had a specific histone acetylation profile and whether the acetylation profile differed for genes with different kinetics of induction.
Publication Title
Defining the chromatin signature of inducible genes in T cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC- on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-) regulates EMT by acting as a critical chromatin-anchored switch for inducible genes. Genome-wide transcriptome analysis identifies a unique cohort of inducible PKC--sensitive genes in MCF7 cells stimulated with phorbol ester.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. The epithelial cell line MCF7, can be induced to undergo EMT with the induction of PKC by PMA. 5-10% of the resulting cells have a CSC phenotype. This study looks at the transcriptome of these cells and how it differs from cells with a non-CSC phenotype.
Publication Title
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Sample Metadata Fields
Cell line, Treatment
View Samples