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GSE44946
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Three master regulatory transcription factors Pdx1, MafA and Ngn3 have the ability to transdifferentiate pancreatic acinar cells to insulin-producing beta cells in mice. BRD7552 was identified as a small-molecule inducer that can upregulate the expression of Pdx1 in PANC-1 cells by high-throughput qPCR screening.
Publication Title
A small-molecule inducer of PDX1 expression identified by high-throughput screening.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 280 Downloadable Samples
Illumina HiSeq 2000
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: IVF was carried out using oocytes from females fed Control diet (C) and sperm from males fed Control diet or Low Protein diet (LP). Zygotes were then developed 2 cell (2C), 4 cell (4C), 8 cell (8C), Morula (M) or Blastocyst (B) embryonic developmental stages when single embryo RNA seq was carried out to study gene expression changes.
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 187 Downloadable Samples
- NextSeq 500
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by IVF from animals fed a control diet. These embryos were then microinjected with various combinations of small RNAs and control RNA (HIS3.3::GFP). Follwoing injections the zygotes were developed and allowed to develop until 2 cell (2C) or 4 cell (4C) stage when single embryo RNA seq was carried out to study gene expression changes
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 103 Downloadable Samples
- NextSeq 500
Description
Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5’ fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes – extracellular vesicles which fuse with sperm during epididymal transit – exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Overall design: Zygotes were generated by ICSI from oocytes/females fed a Control diet and sperm/males fed either a Control or Low Protein diet. The sperm was isolated from either the Rete testis or the Cauda epididymis and injected either as a whole sperm or just the sperm head. Following fertilization by ICSI the zygotes developed for 28 hours (2C stage) and were harvested for single-embryo RNA-Seq.
Publication Title
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Sample Metadata Fields
Cell line, Subject
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
We use the zebrafish embryo model to study the innate immune response against polystyrene particles. Therefore, we injected 700nm polystyrene into the yolk at 2 dpf and took samples at 1 and 3 days post injection. Overall design: This deep sequence study was designed to determine the gene expression profile by polystyrene particle toxicity. RNA was isolated from embryos at 1 and 3 days post injection. Wildtypes zebrafish embryos were micro-injected into the yolk (2dpf) with 1nl of 5mg/ml of 700nm red fluorescent polystyrene particles suspended in PVP (Polyvinylpyrrolidone) (n=3), mock injected with pvp (n=2), or Non-injected as a control (n=3). After injections embryos were transferred into fresh egg water and incubated at 28°C. At 1 and 3 days post injection 10 embryos per group were snap-frozen in liquid nitrogen, and total RNA was isolated using TRIZOL reagent.
Publication Title
Pathway analysis of systemic transcriptome responses to injected polystyrene particles in zebrafish larvae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
FNDC4 is a novel secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in various mouse models of inflammation as well as in human inflammatory conditions. Specifically, subjects with inflammatory bowel disease show increased FNDC4 levels locally at inflamed sites of the intestine. Interestingly, administration of recombinant FNDC4 during colitis development in mice resulted in markedly reduced disease severity compared to mice injected with a control protein. Conversely, mice that lacked Fndc4 showed increased colitis severity. Analysis of binding of FNDC4 to different immune cell types revealed strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro resulted in reduced phagocytosis, improved survival and reduced pro-inflammatory chemokine expression. Hence, treatment with FNDC4 resulted in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized a novel factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.
Publication Title
FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called intestinal barrier proteins. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPAR), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPAR on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPAR-null mice. Treatment with the synthetic PPAR agonist WY14643 served as reference.
Publication Title
PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.
Publication Title
Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here. Overall design: one replicate of RNA Seq data A375, A375R, A375DR vorinostat treated and patient samples pre- post- vorinostat treatment
Publication Title
An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study is to compare gene expression profiles in quiescent RPE1 hTert cells treated with microtubule-stabilizing (paclitaxel) and microtubule-destabilizing poisons (combretastatin A4) Overall design: RPE 1 hTert cells were grown to full confluency, and maintained as such for 5 days to induce quiescence. Quiescent cells were treated with microtubule poisons combretastatin A4 and paclitaxel for 6 or 24 hours. Total RNA was collected and purified using the PureLink RNA Mini Kit (Invitrogen, Thermo Fisher Scientific, USA). RNA concentration and quality were determined using NanoDrop and Bioanalyzer respectively, and 500 ng of purified RNA was used as input for the Illumina TruSeq Stranded mRNA Library Prep Kit (Illumina, USA). Barcoded libraries were pooled and quantitated using KAPA, and single-end sequenced on an Illumina NextSeq (Illumina, USA). RNA-seq reads were mapped using STAR (version 2.1.0j) and processed using HTSeq-count (version 0.6.1). GRCh38 reference genome and transcript annotations were used for gene mapping; Entrez Gene identifiers and org.Hs.eg.db database were used for genome wide annotation. Differential gene expression and statistical analysis were performed using edgeR package. Genes with >50 reads per million and a fold change significantly different from zero in Wilcoxon signed-rank test (p< 0.05), were marked as differentially expressed genes, based on three biological replicates.
Publication Title
Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues.
Sample Metadata Fields
Specimen part, Subject
View Samples