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GSE30192
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been shown to play a key role in regulating the progressional changes in transcription necessary for muscle differentiation. In this study, we demonstrate that treatment of murine C2C12 mesenchymal progenitor cells with 10 M of the DNA methylation inhibitor 5-azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myotubes. Specifically, 5AC treatment resulted in the upregulation of muscle genes at the myoblast stage while at later stages nearly 50 % of the 5AC-treated myotubes displayed a mature, well-defined sarcomere organization as well as spontaneous contractions that coincided with action potentials and intracellular calcium transients. Both the percentage of striated myotubes and their contractile activity could be inhibited by 20 nM TTX, 10 M ryanodine and 100 M nifedipine, suggesting that action potential-induced calcium transients are responsible for these characteristics. Our data suggest that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2C12 myotubes from reaching full maturity.
Publication Title
Epigenetics: DNA demethylation promotes skeletal myotube maturation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Glucocorticoids are used for the treatment of inflammatory conditions but they also cause many side-effects.
Publication Title
Glucocorticoids induce gastroparesis in mice through depletion of l-arginine.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. In vitro experiments showed that doxorubicin can induce histone eviction as well as DNA damage, while etoposide can only induce DNA damage. Here, we compare the transcription responses of different tissues to doxorubicin or etoposide treatment in vivo.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: We got interested whether genes of airway basal cells are enriched in COPD.
Publication Title
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: We got interested whether genes of airway basal cells are enriched in sarcoidosis.
Publication Title
BAL Cell Gene Expression Is Indicative of Outcome and Airway Basal Cell Involvement in Idiopathic Pulmonary Fibrosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Gallus gallus
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus [lipopolysaccharide (LPS) or saline], and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change = 2 and FDR = 0.05) in the broiler (N=283) than the Fayoumi (N=85), whereas heat treatment resulted in fewer DEG in broiler (N=22) compared to Fayoumi (N=107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. Overall design: At 22 days of age, divergent chicken breeds (Fayoumi and broiler) were treated with a thermal treatment (heat stress at 35C, or thermoneutral at 25C as a control) for 3.5 hours, then stimulated subcutaneously with an inflammatory stimulus (LPS, or saline as a control) for another 3.5 hours. Chickens were euthanized and spleens were harvested. A total of 32 indivudally coded cDNA libraries were prepared using TruSeq v2 library preparation kit which selects for polyA mRNA. In this 2x2x2 full factorial design with the factors of breed, thermal treatment, and inflammatory stimulus, there were a total of 8 treatment groups. Each treatment group had a total of 4 animal biological replicates. Therefore, a total of 32 individual barcoded samples were sequenced. A total of 8 individually barcoded cDNA libraries were sequenced per lane using the HiSeq Illumina 2500, and we used 4 lanes total. Reads were mapped to Galgal 2.0.
Publication Title
Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
During B cell development the precursor B cell receptor (pre-BCR) checkpoint is thought to increase immunoglobulin k light chain (Igk) locus accessibility to the V(D)J recombinase. Accordingly, pre-B cells lacking the pre-BCR signaling molecules Btk or Slp65 showed reduced germline Vk transcription. To investigate whether pre-BCR signaling modulates Vk accessibility through enhancer-mediated Igk locus topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B cells the k enhancers robustly interact with the ~3.2 Mb Vk region and its flanking sequences. Analyses in wild-type, Btk and Slp65 single and double-deficient pre-B cells demonstrated that pre-BCR signaling reduces interactions of both enhancers with Igk locus flanking sequences and increases interactions of the 3k enhancer with Vk genes. Remarkably, pre-BCR signaling does not significantly affect interactions between the intronic enhancer and Vk genes, which are already robust in pro-B cells. Both enhancers interact most frequently with highly used Vk genes, which are often marked by transcription factor E2a. We conclude that the k enhancers interact with the Vk region already in pro-B cells and that pre-BCR signaling induces accessibility through a functional redistribution of long-range chromatin interactions within the Vk region, whereby the two enhancers play distinct roles.
Publication Title
Pre-B cell receptor signaling induces immunoglobulin κ locus accessibility by functional redistribution of enhancer-mediated chromatin interactions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: study the role of MALT1 auto-proteolysis in T cell receptor mediated activation of NF-kB. Methods: Jurkat cells were generated that express wild type MALT1, the auto-cleavage deficient MALT1-R149A mutant, the catalytic inactive MALT1-C464A mutant or the R149A-C464A double mutant (RACA). Expression of endogenous MALT1 was inactivated using TALEN technology for the Jurkat cells expressing MALT1-R149A (JDM-RA) and MALT1-C464A (JDM-CA). Illumina HISeq 2000 deep sequencing was performed to determine the mRNA profiles for MALT1, JDM-RA, JDM-CA and RACA cells in unstimulated conditions or after treatment with 75ng/ml PMA and 150 ng/ml ionomycin for 3 or 18 hrs. Results: PMA ionomycin stimulation of the MALT1 auto-cleavage defective JDM-RA cells fails to activate NF-kB-dependent transcription like for the MALT1 catalytic inactive JDM-CA cells and the double RACA mutant cells. Conclusion: MALT1 autoproteolysis is essential for transcription of NF-kB target genes Overall design: mRNA profiles of Jurkat expressing MALT1, MALT1-R149A, MALT1-C464A and MALT1-R149A-C464A after 0, 3 and 18 hours of stimulation with PMA and Ionomycin were generated by deep sequencing, in duplicate, using Illumina HISeq 2000
Publication Title
MALT1 auto-proteolysis is essential for NF-κB-dependent gene transcription in activated lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have reported that glycosphingolipids (GSL) might be involved in obesity induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin sensitivity accompanied with improved glycemic control leading to decreased liver steatosis in obese mice. In addition, GSL depletion altered hepatic secretory function. In those studies, ubiquitously acting inhibitors for GSL-biosynthesis have been used to inhibit function of the enzyme Ugcg (UDP-glucose:ceramide glucosyltransferase), catalyzing the first step of the glucosylceramide based GSL-synthesis pathway. In the present study, a genetic approach for GSL deletion in hepatocytes was chosen to achieve full inhibition of GSL synthesis and to prevent possible adverse effects caused by Ugcg-inhibitors. Using the Cre/loxP system under control of the albumin promoter, GSL biosynthesis in hepatocytes and their release into the plasma could be effectively blocked. Deletion of GSL in hepatocytes did not change quantity of bile excretion through the biliary duct. Total bile salt content in bile-, feces- and plasma from mutant mice showed no difference as compared to control animals. Cholesterol concentration in liver-, bile-, feces- and plasma-samples remained unaffected. Lipoprotein concentration in plasma-samples in mutant animals reached similar levels as in their control littermates. No alteration in glucose tolerance after intraperitoneal application of glucose and insulin appeared in mutant animals. A preventive effect of GSL-deficiency on development of liver steatosis after high fat diet feeding could not be observed.
Publication Title
Hepatic glycosphingolipid deficiency and liver function in mice.
Sample Metadata Fields
No sample metadata fields
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