Filters
Technology
Platform
GSE62813
Homo sapiens
13 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib.
Publication Title
Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Background: Epigenetic modifications such as methylation silencing of genes with CpG-island-associated promoters is frequently observed in cancer. Studies regarding the implications of epigenetic modifications in osteosarcoma (OS) have been limited. The epigenetic drug decitabine is a potential re-activator of silenced genes through de-methylation, and is currently undergoing clinical trials for cancer treatment. No study to date has utilized decitabine to modify gene expression in OS-derived cells to identify gene-specific methylation targets that may have therapeutic importance. The objective of this study was to measure the response of the OS cell line, U-2OS, to decitabine treatment both in vitro and in vivo.
Publication Title
Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: identification of apoptotic genes as targets for demethylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A non-functional myosin Vb motor in duodenal enterocytes results in disruption of epithelial cell polarity characterized by complete loss of microvilli and mislocalization of apical brush border proteins in the cytoplasm which finally cause a devastating disease in neonates with severe malabsorption defects accompanied by protracted diarrhea during infancy, classified as microvillus inclusion disease (MVID). The exact mechanisms how loss-of-function of MYO5B induces polarity loss are not completely understood in MVID pathogenesis. Obtaining better insights in cell polarity defects caused by loss of MYO5B, we performed microarray- in combination with protein expression-analysis in an inducible CaCo2 MYO5B RNAi cell system. Surprisingly, in MYO5B-depleted CaCo2 cells, CDH1 coding for the cell adhesion protein E-Cadherin and important for cell adhesion and therefore maintenance of cell polarity, was significantly downregulated. Interestingly, mesenchymal cell markers, specifically Vimentin and N-Cadherin, physiologically not expressed in differentiated epithelium, were upregulated and accompanied by increased phospho-c-jun levels in the nucleus. Importantly phospho-c-jun was also found in nuclei of duodenal enterocytes in MVID patients, indicating loss of MYO5B induces epithelial cell scattering in enterocytes.
Publication Title
Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic and cell polarity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 754 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Heritable genetic variants modify cystic fibrosis (CF) clinical phenotypes, e.g., lung disease, age-of-onset of persistent Pseudomonas aeruginosa (P. aeruginosa), and meconium ileus (MI). Previous genome wide association studies (GWAS) have begun to inform the genetic architecture of CF phenotypes. Analyses of gene expression will complement GWAS, as demonstrated by analyses of gene expression in lymphoblastoid cell lines (LCLs) to identify disease-related pathophysiological processes for non-CF complex traits. In this study, global gene expression was measured in RNA from LCLs from 754 CF patients and analyzed for association with lung disease severity, age-of-onset of persistent P. aeruginosa pulmonary infection, and MI at birth. Each phenotype displayed distinct expression associations. Most pathways significantly associated with lung disease were related to membranes, vesicle traffic, and Golgi/endoplasmic reticulum (ER). Pathways containing HLA genes (Class I and II) were significantly associated with both lung and P. aeruginosa phenotypes, but they displayed qualitative differences between phenotypes. MI associated with pathways involving oxidative phosphorylation. The results support the concept that gene expression associated with heritable variation acts to modify phenotypes in CF.
Publication Title
Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes.
Sample Metadata Fields
Sex
View Samples- Schizosaccharomyces pombe
- 8 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay.
Publication Title
Characterization of zfs1 as an mRNA-binding and -destabilizing protein in Schizosaccharomyces pombe.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Splenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin’s lymphoma that affects 0.13 per 100,000 persons annually. Overall survival of SMZL is estimated to reach 8 to 11 years in most cases, but up to 30% of SMZL cases develop aggressive presentations resulting in greatly diminished time of survival. SMZL presents with a very heterogeneous molecular profile, making diagnosis problematic and accurate prognosis even less likely. The study herein has utilized this data to assist in identifying a potential diagnostic gene expression signature with highly specific predictive utility for further evaluation among control and SMZL patient samples. Delineation of a unique SMZL signature that could provide diagnostic utility for a malignancy that has historically been difficult to identify. These results should be further investigated and validated in subsequent molecular investigations of SMZL so it may be potentially incorporated into standard oncology practice for improving the understanding and outlook for SMZL patients.
Publication Title
Identification of a Splenic Marginal Zone Lymphoma Signature: Preliminary Findings With Diagnostic Potential.
Sample Metadata Fields
No sample metadata fields
View Samples- Glycine max
- 22 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
The paraveinal mesophyll (PVM) of soybean leaves is a layer of laterally expanded cells sandwiched between the palisade and spongy mesophyll chlorenchyma. The vacuoles of PVM cells contain an abundance of a putative vegetative storage protein, VSP (, ). VSP is is constitutively produced, but is up-regulated during sink limitation experiments involving flower, fruit, or vegetative bud removal. Soybean vegetative lipoxygenases (Vlx), consisting of 5 isozymes (Vlx, A-D), have been identified as potential storage proteins because they accumulate to high levels with experimental sink limitation and have been co-localized with VSP to the vacuoles of PVM cells. We re-investigated the sub-cellular locations of these enzymes with TEM immuno-cytochemistry. We employed laser micro-dissection to compared RNA expression of PVM cells with mesophyll chlorenchyma cells, and we performed a micro-array analysis of soybean leaf samples representing a time-course, sink-limitation, experiment. We found that none of the Vlx isozymes co-localize with putative storage proteins in PVM vacuoles, and that our sink limitation experiment (typical of those used in the past) induced a strong up-regulation of stress response genes, simultaneous with the up-regulation of the Vlx isozymes. Our findings do not support a storage function for soybean Vlx.
Publication Title
Experimental sink removal induces stress responses, including shifts in amino acid and phenylpropanoid metabolism, in soybean leaves.
Sample Metadata Fields
Specimen part, Disease
View Samples- Glycine max
- 6 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
The paraveinal mesophyll (PVM) of soybean leaves is a layer of laterally expanded cells sandwiched between the palisade and spongy mesophyll chlorenchyma. The vacuoles of PVM cells contain an abundance of a putative vegetative storage protein, VSP (, ). VSP is is constitutively produced, but is up-regulated during sink limitation experiments involving flower, fruit, or vegetative bud removal. Soybean vegetative lipoxygenases (Vlx), consisting of 5 isozymes (Vlx, A-D), have been identified as potential storage proteins because they accumulate to high levels with experimental sink limitation and have been co-localized with VSP to the vacuoles of PVM cells. We re-investigated the sub-cellular locations of these enzymes with TEM immuno-cytochemistry. We employed laser micro-dissection to compared RNA expression of PVM cells with mesophyll chlorenchyma cells; and we performed a micro-array analysis of soybean leaf samples representing a time-course, sink-limitation, experiment. We found that none of the Vlx isozymes co-localize with putative storage proteins in PVM vacuoles, and that our sink limitation experiment (typical of those used in the past) induced a strong up-regulation of stress response genes, simultaneous with the up-regulation of the Vlx isozymes. Our findings do not support a storage function for soybean Vlx.
Publication Title
Experimental sink removal induces stress responses, including shifts in amino acid and phenylpropanoid metabolism, in soybean leaves.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 232 Downloadable Samples
Illumina HiSeq 2500
Description
We performed Fluidigm C1 single cell sequencing analysis of wild-type and microRNA deficient (Dgcr8 knockout) mouse embryonic stem cells mock treated or transfected with either miR-294 or let-7. Overall design: Wild-type and Dgcr8 knockout cells grown in naïve culture conditions were mock transfected or transfected with miRNA mimics for let-7b or miR-294, single cells were captured on Fluidigm C1 24 hours post-transfection and then prepared for sequencing on Illumina HiSeq1000 following manufacturer''s protocol.
Publication Title
The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
LDL or Ox-LDL 200ug/ml, which showed no loss of viability after a 48 hour exposure, induced a physiological and pathological transcriptional response, respectively. LDL induced a downregulation of genes associated with cholesterol biosynthesis while ox-LDL induced transcriptional alterations in genes related to inflammation, matrix expansion, lipid metabolism and processing, and apoptosis. Pentraxin-3 was secreted into the culture medium after RPE cells were stimulated with ox-LDL, and immunohistochemically evident in Bruchs membrane of human macular samples with age-related macular degeneration. ARPE-19 cells exposed to 200?g/ml ox-LDL had a 38% apoptosis rate compared to less than 1% when exposed to LDL or untreated controls (p<0.0001).
Publication Title
Oxidized low density lipoproteins induce a pathologic response by retinal pigmented epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples