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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
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
AZD1208 is a novel PIM kinase inhibitor that we have shown inhibits tumorigenesis in tissue recombination models, Myc-CaP allograft models, and human prostate cancer xenografts. We sought to determine the intracellular pathways that are responsible for the anti-tumor effect. To this end we used the tissue recombination protocol to implant MYCCaP cells into castrated mice. MYCCaP cells are an androgen-dependent mouse cell line that overexpresses the oncogene MYC. The mice used for implantation were castrated, so any tumors that result from the grafting procedure are androgen-independent. The grafted mice were divided into a control population receiving vehicle, and a test population receiving AZD1208. The tumors were harvested and in vitro cell lines were made. The new cell lines have been perpetuated in androgen-depleted media.
Publication Title
PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET triple knockdown cells to control cells treated with non-targeting siRNAs to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Rationale: MicroRNAs play key roles in hypertrophic stress responses. miR-378(-3p) is a highly abundant, cardiomyocyte-enriched microRNA whose downregulation in pressure-overload has been suggested as detrimental to the heart. Previous studies have utilized systemic anti-miR or microRNA-encoding virus administration, and thus questions regarding the cardiomyocyte-autonomous roles of miR-378 remain. Objective: To examine whether persistent overexpression of miR-378 in cardiomyocytes alters the phenotype of the unstressed heart, whether its overexpression is beneficial or deleterious in the setting of pressure-overload, and to comprehensively identify its cardiomyocyte-specific effects on mRNA regulation. Methods and Results: Cardiac function was compared in young (10-12 week-old) mice overexpressing miR-378 in the heart under the control of the Myh6 promoter (alphaMHC-miR-378 mice), in older (40 week-old) mice and their age-matched wild-type controls. Older alphaMHC-miR-378 mice exhibited decreased fractional shortening and modest chamber dilation with an increase in cardiomyocyte length. When subjected to pressure-overload, cardiomyocyte length was increased in young alphaMHC-miR-378 mice, but fractional shortening declined precipitously over two weeks. Transcriptome profiling of wild-type and alphaMHC-miR-378 hearts in unstressed and pressure-overload conditions revealed dysregulation of several upstream metabolic and mitochondrial genes in alphaMHC-miR-378 hearts, compromising the reprogramming that occurs during early adaptation to pressure overload. Ago2 immunoprecipitation with mRNA sequencing revealed novel miR-378 cardiac mRNA targets including Akt1 and Epac2 and demonstrated the contextual nature of previously described miR-378 targeting events. Conclusions: Long-term upregulation of miR-378 levels in the heart is not innocuous and exacerbates contractile dysfunction in pressure-overload hypertrophy through numerous signaling mechanisms. Overall design: Cardiac polyadenylated RNA (mRNA) or RISC-seq (total RNA-seq of Ago2 immunoprecipitate) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 2 weeks of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 3 transgenic sham, 7 nontransgenic TAC, 7 transgenic TAC, each with mRNA-seq and RISC-seq data.
Publication Title
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
Description
miR-133a-3p is a highly abundant cardiomyocyte-enriched microRNA whose expression is persistently decreased in response to pressure overload (or transverse aortic constriction, TAC) in mice. Overexpression of miR-133a in cardiomyocytes of mouse hearts in vivo (under the control of the Myh6 promoter) decreases pressure overload-induced apoptosis and fibrosis. In previous studies using microarray platforms, we detected numerous mRNAs whose transcript levels were altered by either or both of miR-133a overexpression and pressure overload. The data set presented here builds upon our previous study in these mice by examining mRNA-RISC associations (using Ago2-immunoprecipitated RNA) and global mRNA abundances via RNA-sequencing procedures, and tests the hypothesis that mRNAs targeted by overexpressed miR-133a are dissimilar between sham and TAC contexts. Overall design: Cardiac polyadenylated RNA (mRNA) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 1 week of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 7 transgenic sham, 5 nontransgenic TAC, 4 transgenic TAC, each with mRNA-seq and RISC-seq (mRNA-seq of Ago2 immunoprecipitate) data.
Publication Title
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Androgenic steroids are increasingly used for hormone therapy of postmenopausal women and abused as life style drugs and for doping purposes, though knowledge about associated health risks in females is very limited. In order to understand more about short- and long-term androgen effects on a molecular level, we have analyzed hepatic gene expression in female C57BL/6 mice immediately after subcutaneous treatment with testosterone for 3 weeks and after 12 weeks hormone withdrawal using Affymetrix array technology and quantitative real-time RT-PCR. Among about 14,000 genes examined, 48 were up- and 65 genes were downregulated by testosterone after 3-weeks treatment and about 50% of these changes persisted even 12 weeks after testostrone withdrawal. In addition to obvious risks such as induction of hepatocellular carcinomas and virilization of liver metabolism, testosterone induced a series of changes, as e.g. dysregulation of hepatic gene expression due to incomplete conversion of female to male phenotype in particular downregulation of cytochrom P450 isoforms and sulfotransferases. As a long-term testosterone effect, transcripts emerged in the liver that are normally specific for the exocine pancreas including amylase 2, ribonuclease 1, and several trypsin-, chymotrypsin-, and elastase-like proteases. This transdifferentiation of hepatic to exocrine pancreatic tissue indicates that testosterone can initiate long-lasting differentiation programs, which once induced progress even after androgen withdrawal. This may have far-reaching consequences difficult to foresee implying long-term hazards of testosterone-treatment for female health that have not been taken into account yet.
Publication Title
Testosterone-induced upregulation of miRNAs in the female mouse liver.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarray data to look for gene differentially expressed in the aorta of WT and L-PGDS ko male mice.
Publication Title
Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 81 Downloadable Samples
- Illumina HiSeq 4000
Description
The ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in grafted Arabidopsis thaliana hypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events. Overall design: We analyzed the poly-adenylated transcriptomes of Arabidopsis thaliana hypocotyle tissue during grafting. Our dataset contains 82 strand-specific samples, whereas each condition is represented by two biological replicates.
Publication Title
Transcriptome dynamics at <i>Arabidopsis</i> graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.
Sample Metadata Fields
Subject
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