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GSE20015
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2.
Publication Title
Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes, however, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and muscle molecular circadian clock have never been investigated in humans. Here we investigated insulin sensitivity and muscle metabolism in fourteen healthy young lean men (age 22.4 2.8 years; BMI 22.3 2.1 kg/m2 [mean SD]) after a 3-day control protocol and a 3.5-day misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that circadian misalignment results in a significant decrease in peripheral insulin sensitivity due to a reduced skeletal muscle non-oxidative glucose disposal (Rate of disappearance: 23.7 2.4 vs. 18.4 1.4 mg/kg/min; control vs. misalignment; p=0.024). Fasting glucose and FFA levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the new behavourial rhythm, and microarray analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misallignement. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.
Publication Title
Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle.
Sample Metadata Fields
Sex, Subject
View Samples- Macaca mulatta, Chlorocebus aethiops, Homo sapiens, Macaca fascicularis
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling is an important tool in the development of medical countermeasures against chemical warfare agents (CWAs). Non-human primates (NHPs), specifically the rhesus macaque (Macaca mulatta), the cynomologus macaque (Macaca fascicularis) and the African green monkey (Chlorocebus aethiops), are vital models in the development of CWA prophylactics, therapeutics, and diagnostics. However, gene expression profiling of these NHPs is complicated by the fact their genomes are not completely sequenced, and that no commercially available oligonucleotide microarrays (genechips) exist. We, therefore, sought to determine whether gene expression profiling of NHPs could be performed using human genechips. Whole blood RNA was isolated from each species and used to generate genechip probes. Hybridization of the NHP samples to human genechips (Affymetrix Human U133 Plus 2.0) resulted in comparable numbers of transcripts detected compared with human samples. Statistical analysis revealed intraspecies reproducibility of genechip quality control metrics; interspecies comparison between NHPs and humans showed little significant difference in the quality and reproducibility of data generated using human genechips. Expression profiles of each species were compared using principal component analysis (PCA) and hierarchical clustering to determine the similarity of the expression profiles within and across the species. The cynomologus group showed the least intraspecies variability, while the human group showed the greatest intraspecies variability. Intraspecies comparison of the expression profiles identified probesets that were reproducibly detected within each species. Each NHP species was found to be dissimilar to humans; the cynomologus group was the most dissimilar. Interspecies comparison of the expression profiles revealed probesets that were reproducibly detected in all species examined. These results show that human genechips can be used for expression profiling of NHP samples and provide a foundation for the development of tools for comparing human and NHP gene expression profiles.
Publication Title
Comparison of non-human primate and human whole blood tissue gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Zea mays
- 8 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
ABSTRACT: BACKGROUND: While changes in chromosome number that result in aneuploidy are associated with phenotypic consequences such as Down syndrome and cancer, the molecular causes of specific phenotypes and genome-wide expression changes that occur in aneuploids are still being elucidated. RESULTS: We employed a segmental aneuploid condition in maize to study phenotypic and gene expression changes associated with aneuploidy. Maize plants that are trisomic for 90% of the short arm of chromosome 5 and monosomic for a small distal portion of the short arm of chromosome 6 exhibited a phenotypic syndrome that includes reduced stature, tassel morphology changes and the presence of knots on the leaves. The knotted-like homeobox gene knox10, which is located on the short arm of chromosome 5, was shown to be ectopically expressed in developing leaves of the aneuploid plants. Expression profiling revealed that ~40% of the expressed genes in the trisomic region exhibited the expected 1.5 fold increased transcript levels while the remaining 60% of genes did not show altered expression even with increased gene dosage. CONCLUSIONS: We found that the majority of genes with altered expression levels were located within the chromosomal regions affected by the segmental aneuploidy and exhibits dosage-dependent expression changes. A small number of genes exhibit higher levels of expression change not predicted by the dosage, or display altered expression even though they are not located in the aneuploid regions.
Publication Title
Profiling expression changes caused by a segmental aneuploid in maize.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 106 Downloadable Samples
Illumina HiSeq 2000
Description
The CCA-adding enzyme adds CCA to the 3'' ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3'' ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. Here, we report deep sequencing analysis of the 3'' ends of tRNA-Ser-CGA and tRNA-Ser-UGA from S. cerevisiae strains and show that hypomodified mature tRNAs are subjected to CCACCA (or poly(A) addition) as part of a rapid tRNA decay pathway in vivo. We conjecture that CCACCA addtion is a universal mechanism for controlling tRNA levels and preventing errors in translation. Overall design: 121 samples analyzed in total, representing time courses of 10 different yeast strains; Biological replicates for each time point are included
Publication Title
tRNAs marked with CCACCA are targeted for degradation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5'' UTR. mTORC1 also controls ATF4 translation through uORFs, but independent of changes in eIF2a phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery. Overall design: RNA-seq analysis of wild-type and ATF4-null HEK293T cells treated with Torin 1 or tunicamycin for 6 h, and ribosome profiling analysis of HEK293T cells treated with Torin 1 for 24 h.
Publication Title
mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional profiling of IAS subjects
Publication Title
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 88 Downloadable Samples
- Illumina HiSeq 2500
Description
Cg.5XFAD females (MMRRC Stock No #34848-JAX) were bred to males from BXD strains. The resulting F1 progeny were monitored throughout their lifepan to evaluate the effect of genetic background on cognitive and pathological traits. Samples here come from various AD-BXD lines at either 6 or 14 months of age. An earlier dataset of similar design (plus Non-transgenic littermates) was deposited as GSE101144. Ntg littermates of mice sampled here will be deposited as a separate GEO series. Overall design: 88 AD samples. For final by-strain analysis, samples were averaged into strain/age/genotype/sex groups (For example, all D2 6mo 5XFAD males were averaged for final by-strain analysis)
Publication Title
Identification of Pre-symptomatic Gene Signatures That Predict Resilience to Cognitive Decline in the Genetically Diverse AD-BXD Model.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
RDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur either occupationally or through ordnance that lays unexploded on training ranges. The toxicology of RDX is dominated by acute tonic-clonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Sub-chronic studies have revealed few other toxic effects. The objective of this study was to examine the effect of a single oral dose of RDX on global gene expression in the mammalian brain and liver, using a rodent model.
Publication Title
Global gene expression in rat brain and liver after oral exposure to the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).
Sample Metadata Fields
No sample metadata fields
View Samples