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GSE30873
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Caspase-8 is a cystein protease involved in regulating apoptosis. The function of caspase-8 was studied in the intestinal epithelium, using mice with an intestinal epithelial cell specific deletion of caspase-8.
Publication Title
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors.
Publication Title
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 2500
Description
Cancer cells alter their metabolism to support their malignant properties. By transcriptomic analysis we identified the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) as strongly correlated with epithelial-to-mesenchymal transition (EMT). This association was confirmed staining samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing profiling confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGF-Beta signature genes. Mechanistically, excess glucose was found to promote EMT through autocrine TGF-Beta stimulation, while PP-deficient cells were refractory to glucose-induced EMT. PP represents a molecular link between glucose metabolism and cancer differentiation and aggressiveness, and a novel potential therapeutic target. Overall design: 3x3 biological replicated samples; 2 groups of samples with shRNA-mediated specific gene inhibition and scrambled control cells
Publication Title
Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 1 Downloadable Sample
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 5 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to impaired expression of IFN--inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that repeated short-term co-cultures of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-1 (26-35)-specific CTL led to the generation of clones resistant to CTL-mediated cell death. To determine which of the UPS components and its associated pathways was responsible for CTL escape; three UKRV-Mel-15a clones were subjected to microarray gene expression analysis.
Publication Title
Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 3 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human epidermal keratinocytes were treated with 25 ng.ml EphB2 or EFNA4, both as-Fc conjugates (Sigma).
Publication Title
Eph-2B, acting as an extracellular ligand, induces differentiation markers in epidermal keratinocytes.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Skeletal muscle constitutes a significant portion of total body mass and is a major regulator of systemic metabolism as it serves as the major site for glucose disposal and the main reservoir for amino acids. With aging, cachexia, starvation, and myositis, there is a preferential loss of fast glycolytic muscle fibers. We previously reported a mouse model in which a constitutively-active Akt transgene is induced to express in a subset of muscle groups leading to the hypertrophy of type IIb myofibers with an accompanying increase in strength. This muscle growth protects mice in various cardio-metabolic disease models, but little is known about the underlying cellular and molecular mechanisms by which fast-twitch muscle impacts disease processes and regulates distant tissues. Purpose: In the present study, poly(A)+ tail mRNA-seq was performed to characterize the transcriptome of the hypertrophic gastrocnemius muscle from Akt1-transgenic mice. Results: Pathway analysis for the 3,481 differentially expressed genes in muscle identified enriched signaling pathways involving growth, cell cycle regulation, and inflammation. Combined metabolomics and transcriptomic analyses revealed that Akt1-induced muscle growth mediated a metabolic shift involving reductions in glycolysis and oxidative phosphorylation, but enhanced pentose phosphate pathway activation and increased branch chain amino acid accumulation. Signal peptide prediction analysis revealed 241 differentially expressed in muscle transcripts that potentially encode secreted proteins. A number of these secreted factors have signaling properties that are consistent with the myogenic, metabolic and cardiovascular-protective properties that have previously been associated with type IIb muscle growth. Conclusions: These data reveal that enhanced Akt signaling promotes the activation of the pentose phosphate and the accumulation of branched amino acids that are important for the production of nucleic acids and proteins. Numerous known and novel transcripts potentially encoding muscle secreted proteins were identified, indicating the importance of fast-twitch muscle in inter-tissue communication. Overall design: mRNA profiles of adult muscle growth from four muscle-specific conditional Akt transgenic (DTG) and four littermate control mice (1256[3Emut]Mck-rtTA) were generated by deep sequencing using Illumina HiSeq.
Publication Title
RNA-seq and metabolomic analyses of Akt1-mediated muscle growth reveals regulation of regenerative pathways and changes in the muscle secretome.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Both ephrins and their receptors are membrane bound, restricting their interactions to the sites of direct cell-to-cell interfaces. They are widely expressed, often co-expressed and regulate developmental processes, cell adhesion, motility, survival, proliferation, and differentiation. Both tumor suppressor and oncogene activities are ascribed to EFNs and Ephs in various contexts. A major conundrum regarding the EFN/Eph system concerns their large number and functional redundancy, given the promiscuous cross-activation of ligands and receptors and the overlapping intracellular signaling pathways. To address this issue, we treated human epidermal keratinocytes with 5 EFNAs individually and defined the transcriptional responses in the cells. We found that a large set of genes is coregulated by all EFNAs. However, while the responses to EFNA3, EFNA 4 and EFNA 5 are identical, the responses to EFNA1 and EFNA2 are characteristic and distinctive. All EFNAs induce epidermal differentiation markers and suppress cell adhesion genes, especially integrins. Ontological analysis shows that all EFNAs induce cornification and keratin genes, while suppressing wound-healing associated, signaling, receptor and ECM associated genes. Transcriptional targets of AP1 are selectively suppressed by EFNAs. EFNA1 and EFNA2, but not the EFNA3, EFNA4, EFNA5 cluster, regulate the members of the ubiquitin-associated proteolysis genes. EFNA1 specifically induces collagen production. Our results demonstrate that the EFN-Eph interactions in the epidermis, while promiscuous, are not redundant but specific. This suggests that different members of the EFN/Eph system have specific, clearly demarcated functions.
Publication Title
Specific and shared targets of ephrin A signaling in epidermal keratinocytes.
Sample Metadata Fields
No sample metadata fields
View Samples