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GSE11496
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In eukaryotes, regulation of mRNA translation enables a fast, localized and finely tuned expression of gene products. Within the translation process, the first stage of translation initiation is most rigorously modulated by the actions of eukaryotic initiation factors (eIFs) and their associated proteins. These 11 eIFs catalyze the joining of the tRNA, mRNA and rRNA into a functional translation complex. Their activity is influenced by a wide variety of extra- and intracellular signals, ranging from global, such as hormone signaling and unfolded proteins, to specific, such as single amino acid imbalance and iron deficiency. Their action is correspondingly comprehensive, in increasing or decreasing recruitment and translation of most cellular mRNAs, and specialized, in targeting translation of mRNAs with regulatory features such as a 5 terminal oligopyrimidine tract (TOP), upstream open reading frames (uORFs), or an internal ribosomal entry site (IRES). In mammals, two major pathways are linked to targeted mRNA translation. The target of rapamycin (TOR) kinase induces translation of TOP and perhaps other subsets of mRNAs, whereas a family of eIF2 kinases does so with mRNAs containing uORFs or an IRES. TOR targets translation of mRNAs that code for proteins involved in translation, an action compatible with its widely accepted role in regulating cellular growth. The four members of the eIF2 kinase family increase translation of mRNAs coding for stress response proteins such as transcription factors and chaperones. Though all four kinases act on one main substrate, eIF2, published literature demonstrates both common and unique effects by each kinase in response to its specific activating stress. This suggests that the activated eIF2 kinases regulate the translation of both a global and a specific set of mRNAs. Up to now, few studies have attempted to test such a hypothesis; none has been done in mammals.
Publication Title
eIF2alpha kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Consumption of a protein containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, a-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), that interconverts leucine and a-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wildtype mice were compared using Next Generation RNA-Sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1486/~39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis (eIF2, mTOR, eIF4 and p70S6K pathways including 40S and 60S ribosomal proteins), protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy and cell death) were up-regulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways were observed in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids and BCAAs were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wildtype mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes. Overall design: Comparison of wildtype and BCATm KO gastrocnemius biological replicates
Publication Title
Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We used a novel approach to study the acute effect of three physiologic stressors (active contractions, vibration, and systemic heat stress) in human skeletal muscle. Three hours after the completion of a dose of physiologic stress, we sampled the soleus (contraction and vibration) or vastus lateralis (heat) muscle and developed a unique gene expression signature for each stressor. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold change), PGC-1 (5.46 fold change), and ABRA (5.98 fold change); and repressed MSTN (0.56 fold change). Heat stress repressed PGC-1 (0.74 fold change); while vibration induced FOXK2 (2.36 fold change). Vibration similarly caused a down regulation of MSTN (0.74 fold change), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 while heat stress repressed PGC-1 (0.74 fold change) and ANKRD1 genes (0.51 fold change). These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
Publication Title
Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Microarray-based DNA methylation and gene expression profiling was carried out using a panel of prostate cancer cell lines (LNCaP-FGC, DU-145, and PC-3) and the control normal prostate RWPE1 cell line. The identification of prostate cancer-specific methylation markers was based on the following criteria: a difference in DNA methylation level () of at least 0.5, and at least a 2-fold difference in expression level between cancer and control cells. Using highly stringent selection criteria, we identified novel hypermethylated genes whose expression was silenced in prostate cancer cells.
Publication Title
EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
The objective of this study is to identify gene signature associated with castration-refractory prostate cancer (CRPC) development. We carried out RNA-seq based transcriptome profiling using 45 prostate samples with various disease progression steps such as benign prostate hyperplasia (BPH), primary cancer of prostate (CaP), advanced CaP and CRPC. Via various statistical analyses, we identified significant gene set associated with each progression step and observed that AR was the only gene feature associated with all progression steps, indicating that AR is the crucial mediator of and has a diverse activity across the CaP progressions. Among the samples in this data set, there are 4 pairs of advanced CaP and CRPC samples, in which each pair was obtained from the same patient. Using these paired samples, we also determined differentially expressed genes between advanced CaP and CRPC, and performed comparative analysis of significant gene lists in matched sample pairs and in unpaired remained samples. By assessing expression difference between advanced CaP and CRPC groups, 309 and 182 genes were statistically significant in paired and unpaired samples, respectively (P < 0.001). When these two gene lists were compared, a total of 15 genes were common and applied to a number of downstream experimental assays. Overall design: RNA-seq data of 45 CRPC samples were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer''s protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x100 bp) using Hiseq-2000 (Illumina).
Publication Title
Transcriptomic features of primary prostate cancer and their prognostic relevance to castration-resistant prostate cancer.
Sample Metadata Fields
Subject
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
There are clear phenotypic differences between Korean native pig (KNP) and Yorkshire (YS) breeds because of different interests for selection. YS has been artificially selected by industrial interests such as a growth rate and a lean meat production, however, KNP has been maintained as a regional breed by local interests such as a fat content in or between muscle and a disease resistance. A comparison of gene expression profile from a major tissue liver can reflect the overall effects of the artificial selection between the two pig breeds through long history. KNP (n=4) and YS (n=4) pigs were raised under the identical conditions. Global gene expression levels were measured in liver samples from these pigs using Affymetrix porcine genome array containing 23,937 probe sets. The clustering analysis based on the individual transcriptome data showed a clear separation between two breeds in the liver tissue. We collected hepato-transcriptome data including 11,993 genes fully detected from four independent samples either in KNP or in YS. Based on both minimum positive false discovery rate (less than 15%) and fold change (|FC| > 1.5), 160 differentially expressed genes (DEGs) were collected from the liver between the two breeds. The functional analysis of these DEGs indicated clear distinctions in intra- and extra-cellular structure, cell proliferation, membrane trafficking, glycolytic pathway, mitochondrial function, protein metabolism, and immune response. The functional characteristics based on the DEGs were useful indicators to explain the differences between these two breeds developed for the specific purposes each other. The hepatic DGEs indicate that the YS has been lost expressivity of genes not required for the fast growth but maintained expressivity of genes for lean muscle production. The tissue-wise gene expression profiles indicate that the liver could be a major place to make the economic distinction between these two pig breeds.
Publication Title
Differences in hepatic gene expression as a major distinguishing factor between Korean native pig and Yorkshire.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2000, IlluminaGenomeAnalyzerIIx
Description
To understand epigenetic changes in the distal regulatory as well as proximal regions, we performed RNA-seq, MBD-seq, and H3K27ac ChIP-seq on gastric tissues and cell lines. Overall design: mRNA sequencing profiles of normal tissue (n), purified gastric cancer (sc), and cultured gastric cancer cell (dc) were generated by deep sequencing, in five samples from three patients (csc1, csc2, csc3) and two replicates (csc1_sc2, csc1_sc3), using Illumina GAIIx and HiSeq2000.
Publication Title
Integrated epigenomic analyses of enhancer as well as promoter regions in gastric cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The pig could be a useful model to characterize molecular aspects determining several delicate phenotypes because they have been bred for those characteristics. The Korean native pig (KNP) is a regional breed in Korea that was characterized by relatively high intramuscular fat content and reddish meat color compared to other western breeds such as Yorkshire (YS). YS grew faster and contained more lean muscle than KNP. We compared the KNP to Yorksire to find molecular clues determining muscle characteristics. The comparison of skeletal gene expression profiles between these two breeds showed molecular differences in muscle. We found 82 differentially expressed genes (DEGs) defined by fold change (more than 1.5 fold difference) and statistical significance (within 5% of false discovery rate). Functional analyses of these DEGs indicated up-regulation of most genes involved in cell cycle arrest, down-regulation of most genes involved in cellular differentiation and its inhibition, down-regulation of most genes encoding component of muscular-structural system, and up-regulation of most genes involved in diverse metabolism in KNP. Especially, DEGs in above-mentioned categories included a large number of genes encoding proteins directly or indirectly involved in p53 pathway. Our results indicated a possible role of p53 to determine muscle characteristics between these two breeds.
Publication Title
Transcriptional alteration of p53 related processes as a key factor for skeletal muscle characteristics in Sus scrofa.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
In order to investigate the role of reptin methylation on the expression of hypoxia-responsive genes across the whole genome, we performed a microarray analysis from RNAs isolated from MCF7 cells expressing either control shRNA (shRNA) or reptin shRNA (shreptin) in normoxic and hypoxic conditions.
Publication Title
Negative regulation of hypoxic responses via induced Reptin methylation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
We established PDX lines from diffuse type gastric cancers (DGCs). Using these cells, we carried out RNA-seq based transcriptome profiling using 15 stomach samples including three PDX lines (HGC-3, HGC-8, and HGC-20) and normal-looking surrounding tissues. Via comparative analysis between cells and tissues, we identified significant gene set associated with each cell and observed that genes involved in AKT signalling pathway were commonly associated with all PDX lines. Overall design: RNA-seq data of 15 gastric samples were generated. Total RNA was isolated by RNeasy Mini Kit (Qiagen, CA, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Sequencing library was prepared using TruSeq RNA Sample Preparation kit v2 (Illumina, CA, USA) according to the manufacturer's protocols. Briefly, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads, fragmented, and converted into cDNAs. Then, adapters were ligated and the fragments were amplified on a PCR. Sequencing was performed in paired end reads (2x75 bp) using Hiseq-2500 (Illumina).
Publication Title
Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer.
Sample Metadata Fields
Subject
View Samples