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GSE27831
Homo sapiens
27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a woundhealing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target.
Publication Title
Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patients age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Illumina HiSeq 2000
Description
Molecular mechanisms underlying terminal differentiation of B-cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here, we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B-cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels but followed by a committal step in which an S-phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Publication Title
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 36 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to facilitating the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, and decreases developmental stability. Further, by quantitative analysis of morphological phenotypes, we demonstrate that HSP90-reduction increases phenotypic diversity in both seedlings and adult plants. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment.
Publication Title
Phenotypic diversity and altered environmental plasticity in Arabidopsis thaliana with reduced Hsp90 levels.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Using a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Publication Title
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Publication Title
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiScanSQ
Description
Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. Overall design: RNA-seq
Publication Title
AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples