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GSE28059
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dysregulation of ceramide synthesis has been associated with metabolic disorders such as atherosclerosis and diabetes mellitus. Using a human hepatoma cell line (Huh7), we investigated the changes in lipid homeostasis and gene expression when the synthesis of ceramide is perturbed by knocking down serine transferases subunits 1, 2 and 3 (SPTLC123) or dihydroceramide desaturase (DEGS1). While the inhibition of serine palmitoyl transferase (SPTLC) affects ceramide production differently at the subspecies level depending upon which SPTLC subunit is silenced; depleting DEGS1 is sufficient to produce a similar outcome as knocking down all SPTLC subunits. Both the distribution of multiple lipid classes, especially at the subspecies level, and the global transcriptional profile is altered differently when either SPTLC123 or DEGS1 were silenced. The overall transcriptional changes indicate a negative regulation in biosynthetic processes and a down-regulation of genes involved in general endomembrane trafficking for both DEGS1 and SPTLC123 siRNA treated cells, but also the up-regulation of genes involved with cell migration function in DEGS1 siRNA cells. Pathway analysis indicate changes in amino acid, sugar and nucleotide metabolisms as well as vesicle trafficking between organelles occurred more robustly in DEGS1 silenced cells. Although either SPTLC123 or DEGS1 siRNA treatment positively regulated numerous genes involved with endocytosis and endosomal recycling, depleting SPTLC123 caused transcriptional changes in genes primarily involved with lipid metabolism. The alterations reflect how SPTLC or DEGS1 silenced cells respond differently to disruption in lipid flux, but also maintain cellular lipid pools through increasing endocytotic processes and down-regulating metabolic biosynthesis without developing endoplasmic reticulum stress. Also, these results are the first to demonstrate that reducing ceramide synthesis by decreasing the function of either SPTLC or DEGS1 affects cellular function differently at the level of lipid synthesis and gene expression.
Publication Title
Silencing of enzymes involved in ceramide biosynthesis causes distinct global alterations of lipid homeostasis and gene expression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist.
Publication Title
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Two rat hepatic cell lines, WB-F344 and WB311, were characterized for the effect of rapamycin on gene expression. The WB311 cell line, which is tumorigenic and resistant to the growth inhibitory effects of rapamycin, was originally derived from the WB-F344 parental hepatic epithelial cell line. The goal of this experiment was to identify genes that responded to rapamycin in the sensitive cells but not the resistant cells, thereby providing insight into the mechanism of rapamycin resistance.
Publication Title
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2000
Description
The interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNFa, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ERa), the pioneer factor FoxA1 and the p65 subunit of the NF-?B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNFa signaling at the gene level is also evident in the patterns of ERa and NF-?B binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ERa binding sites is predetermined prior to estrogen treatment, whereas ERa binding sites gained upon co-treatment with TNFa require NF-?B and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNFa signaling recruits FoxA1 and NF-?B to latent ERa enhancer locations and directly impact ERa enhancer accessibility. Binding of ERa to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer. Overall design: Using GRO-seq and ChIP-seq (ER, FoxA1 and p65) to assay the molecular crosstalk of MCF-7 cells treated with E2, TNFa or both E2+TNFa.
Publication Title
TNFα signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Infection of RAW264.7 cells with RHku80 parasites or mock-infection for 24 hours
Publication Title
Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A gene expression profile of BRCAness was defined in publicly available expression data of 61 patients with epithelial ovarian cancer (34 patients with BRCA-1 or BRCA-2 mutations and 27 patients with sporadic disease). This dataset is publicly available at http://jnci.oxfordjournals.org/cgi/content/full/94/13/990/DC1
Publication Title
Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.
Sample Metadata Fields
Age, Disease stage
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Liver transplantation is the only therapeutic option for patients with end-stage liver disease. The shortage of donor organs has led to the search for alternative therapies to restore liver function and bridge patients to transplantation. Our previous work has shown that the proliferation of late gestation E19 fetal hepatocytes is mitogen-independent. This is manifested as differences in the control of ribosome biogenesis, global translation, cell cycle progression and gene expression. In the present study, we investigated whether E19 fetal hepatocytes would engraft and repopulate an injured adult liver.
Publication Title
Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Transcriptome of murine testis from wild type mice and mice lacking telomerase for three generations (G3-Terc), Ku86 or both telomerase and Ku86.
Publication Title
Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
strand specific sequencing of RNAs from MAoECs to determine the endothelial-specific expression profile of protein-coding and long non-coding RNAs Overall design: Total RNA was isolated from cultured MAoECs (passage 4) and processed for a strand-specific RNA sequencing. The RNA purity and integrity were assessed using the Fragment Analyzer Automated CE System (Advanced Analytical). A RQN of 8.8 and a 28S/18S ratio of 2.2 were considered acceptable for next generation sequencing assay. Five µg of DNase-treated RNA were used to prepare Massive Analysis of cDNA ends (MACE) libraries needed to perform a DNA-Methylation-Sequencing (Meth-Seq) PCR bias free quantification with TrueQuant Technology, followed by a high-throughput sequencing on the Illumina Genome Analyzer II system (GenXPro GmbH, Frankfurt, Germany). The procedure consist in the extraction of poly-adenylated RNA from 5 µg RNA and reverse transcribed with biotinylated poly(T) primers. cDNA is fragmented to an average size of 250 bp. Biotinylated ends are captured by streptavidin beads and ligated to modified adapters (TrueQuant DNA adapter, GenXPro). The libraries are amplified by PCR, purified by SPRI beads and sequenced (2 x 100 bp Illumina HiSeq2000 TrueSeq, 2 x 20 Mio. Reads poly-A selected paired-end reads). Paired end sequencing of both DNA strands from each end is required for fragment strand specificity.
Publication Title
miR-103 promotes endothelial maladaptation by targeting lncWDR59.
Sample Metadata Fields
Specimen part, Subject
View Samples