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Mus musculus
8 Downloadable Samples
Illumina HiSeq 2000
Description
Objective: Dyslipidemia is one of the key factors behind coronary heart disease. Blood and lymphatic vessels play pivotal roles in both lipoprotein metabolism and development of atherosclerotic plaques. Recent studies have linked members of Vascular Endothelial Growth Factor (VEGF) family to lipid metabolism but the function of VEGF-D has remained unexplored. Here we investigated how the deletion of VEGF-D affects lipid and lipoprotein metabolism in atherogenic LDLR-/-ApoB100/100 mice. Approach and Results: Deletion of VEGF-D (Vegfd-/-LDLR-/-ApoB100/100) led to markedly elevated plasma cholesterol and triglyceride levels without an increase in atherogenesis. Size distribution and hepatic lipid uptake studies confirmed a delayed clearance of large chylomicron remnant particles that cannot easily penetrate through the vascular endothelium. Mechanistically, the inhibition of VEGF-D signaling significantly decreased the hepatic expression of syndecan 1 (SDC1), which is one of the main receptors for chylomicron remnant uptake when LDLR is absent. Immunohistochemical staining confirmed reduced expression of SDC1 in the sinusoidal surface of hepatocytes in VEGF-D deficient mice. Furthermore, hepatic RNA sequencing revealed that VEGF-D is also an important regulator of genes related to lipid metabolism and inflammation. The lack of VEGF-D signaling via VEGF receptor 3 led to lowered expression of genes regulating triglyceride and cholesterol production as well as downregulation of peroxisomal ß-oxidation pathway. Conclusions: These results demonstrate that VEGF-D, a powerful lymphangiogenic and angiogenic growth factor, is also a major regulator of chylomicron metabolism in mice. Overall design: Gene expression profiling of mouse liver tissue from control and VEGF-D knock-out mice. Control and VEGF-D KO mice were both in C57Bl/6 and atherosclerotic background, i.e., deficient of LDLR and expressing only apolipoprotein B100.
Publication Title
Deletion of Lymphangiogenic and Angiogenic Growth Factor VEGF-D Leads to Severe Hyperlipidemia and Delayed Clearance of Chylomicron Remnants.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 20 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Small RNA libraries from total RNA isolated from adult ovaries Overall design: Small RNA libraries were derived from Ovaries of the Founder strain and their offspring and their reciprocal offspring. RNA from 5 individual ovaries was pooled .
Publication Title
piRNA dynamics in divergent zebrafish strains reveal long-lasting maternal influence on zygotic piRNA profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
C.elegans small RNAs from HA::ALG-1, HA::ALG-2 and HA::RDE-1 IP and rde-1 mutants Overall design: Small RNAs were cloned from transgenic or mutant C. elegans adults. Sequencing was performed using 454 and Illumina platforms.
Publication Title
MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Sus scrofa
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
So far, the majority of research on piRNAs was carried out in popular model organisms such as fruit fly and mouse, which however do not closely reflect human PIWI biology. Thus, we high-throughput sequenced and computationally analyzed piRNAs expressed in the adult testis of the pig owing to its full set of mammalian Piwi paralogs, availability for repeat experiments and the existence of elementary data from previous studies on the porcine PIWI/piRNA system. We provide an exhaustive characterization of porcine piRNAs and genomic piRNA clusters. In addition, we reveal that a considerable proportion of piRNAs matches protein coding genes, exhibiting characteristics that point to a biogenesis within the post-transcriptional silencing mechanism of the PIWI/piRNA pathway, commonly referred to as ping pong cycle. We further show that the majority of identified piRNA clusters spans exonic sequences of protein-coding genes or pseudogenes, which indicates the existence of different mechanisms for the generation of piRNAs directed against mRNA. Our data provides evidence that spliced mRNAs, derived from such loci, are not only targeted by piRNAs but are also subject to ping pong cycle processing. Finally, we demonstrate that homologous genes are targeted by piRNAs in pig, mouse and human. Altogether, this strongly suggests a role for mammalian piRNA clusters in gene regulation alongside of TE repression.
Publication Title
piRNAs from Pig Testis Provide Evidence for a Conserved Role of the Piwi Pathway in Post-Transcriptional Gene Regulation in Mammals.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Publication Title
Characterization of genetic loss-of-function of Fus in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Purpose: To examine and characterize the expression profile of genes expressed at the neuromuscular junctions (NMJs) of extraocular muscles (EOMs) in comparison to the NMJs of tibialis anterior muscle (TA).
Publication Title
Identification of the neuromuscular junction transcriptome of extraocular muscle by laser capture microdissection.
Sample Metadata Fields
Specimen part
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SRP001455- Caenorhabditis elegans
- 20 Downloadable Samples
- Illumina Genome Analyzer
Description
High throughput sequencing to derive function of cde-1 in endogenous RNAi in C. elegans Overall design: Small RNAs were cloned from C. elegans adults, following removal of tri-phosphate groups from 5'' end. Sequencing was performed using the Illumina 1G platform.
Publication Title
CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The key lipid metabolism transcription factor sterol regulatory element-binding protein (SREBP)-1a integrates gene regulatory effects of hormones, cytokines, nutrition and metabolites as lipids, glucose or cholesterol via stimuli specific phosphorylation by different MAPK cascades. We have formerly reported the systemic impact of phosphorylation in transgenic mouse models with liver-specific overexpression of the N-terminal transcriptional active domain of SREBP-1a (alb-SREBP-1a) or a MAPK kinase phosphorylation sites deficient variant (alb-SREBP-1aP; (S63A, S117A, T426V)), respectively. Here we investigated the molecular basis of the systemic observation in holistic hepatic gene expression analyses and lipid degrading organelles involved in the pathogenesis of metabolic syndrome, i.e. peroxisomes, by 2D-DIGE and mass spectrometry analyses. Although alb-SREBP-1a mice develop a severe phenotype with visceral adipositas and hepatic lipid accumulation featuring a fatty liver, the hepatic differential gene expression and alterations in peroxisomal protein patterns compared to control mice were surprisingly relative low. In contrast, phosphorylation site deficient alb-SREBP-1aP mice, protected from hepatic lipid accumulation phenotype, showed gross alteration in hepatic gene expression and peroxisomal proteome. Further knowledge based analyzes revealed that overexpression of SREBP-1a favored mainly acceleration in lipid metabolism and indicated a regular insulin signaling, whereas disruption of SREBP-1a phosphorylation resulted in massive alteration of cellular processes including signs for loss of lipid metabolic targets. These results could be the link to a disturbed lipid metabolism that overall resembles a state of insulin resistance.
Publication Title
Inactivation of SREBP-1a Phosphorylation Prevents Fatty Liver Disease in Mice: Identification of Related Signaling Pathways by Gene Expression Profiles in Liver and Proteomes of Peroxisomes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples SRP008008- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
small RNA libraries from total RNA isolated from young adult animals Overall design: Wild-type and rem-1 mutant animals were used for RNA isolation. Regular libraries were made using adaptor ligations at both ends. In addition, librraies were made from oxidised and TAP treated RNA.
Publication Title
Differential impact of the HEN1 homolog HENN-1 on 21U and 26G RNAs in the germline of Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples SRP009275- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
small RNA libraries from wild-type and Hen1 mutant testes were made with either polyA tailing (VASAGFPHen1minus/plus) or adapter ligation (Hen1Testis and WTTestis) and sequenced on an Illumina GAII platform. Overall design: RNA was isolated from total testis tissue of both Hen1 wildtype and Hen1 mutant animals. After size selection from gel, the small RNA libraries wre made.
Publication Title
Hen1 is required for oocyte development and piRNA stability in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples