Filters
Technology
Platform
GSE45997
Rattus norvegicus
9 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Abstract Background Traumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and nave (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI. Results Inspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH. Conclusions Bioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development.
Publication Title
Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Nevirapine alone produces only mild hepatic hypertrophy in the rat. Single ip dose galactosamine produces transient hepatocellular apoptotic and oncotic cell death mimicking viral hepatitis with portal inflammatory infiltrate and biliary hypertrophy and hyperplasia. Damage is typically resolved within 7-10 days. However if rats are pretreated with nevirapine at specific doses for 7 days prior to the single galactosamine dose, bridging fibrosis is observed, 8 days after the single galactosamine dose is given.
Publication Title
Drug-induced Liver Fibrosis: Testing Nevirapine in a Viral-like Liver Setting Using Histopathology, MALDI IMS, and Gene Expression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina HiSeq 2500
Description
We compare the transcription profiles of IL-5-reporter marked ILC2s and Th2 cells sorted from mouse lung tissue after Nippostrongylus brasiliensis infection Overall design: mRNA sequencing comparing material from 2 cell populations sorted from the lungs of 7 Red5/Red5 mice, comprising 2 independent infections, 14 days after N.b. infection
Publication Title
A tissue checkpoint regulates type 2 immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 4000
Description
Sequencing data related to the manuscript entitled, "CD22 blockade restores homeostatic microglial phagocytosis in the aging brain." Overall design: To assess the transcriptional effects of CD22 blockade, we implanted aged mice with osmotic pumps to continuously infuse a CD22 blocking antibody or an IgG control antibody directly into the cerebrospinal fluid for one month. Following one month of continuous infusion, we performed RNA-seq on purified microglia from the hemi-brains of these mice contralateral to the cannulation site to minimize injury-induced confounding factors. Primary mouse microglia were isolated by gentle dounce homogenization of the brain, magentic myelin removal, and FACS-purification of ~20,000 live CD11b+CD45lo cells. Microglia were sorted into RLT Plus buffer (Qiagen) containing beta-mercaptoethanol. RNA was extracted using a RNeasy Micro Plus kit (Qiagen) according the manufacturer's protocol. RNA integrity was assessed on a Bioanalyzer (Agilent), and high quality samples were used for library preparation. cDNA synthesis and amplification was performed using the SmartSeq v4 Ultra-low input kit (Takara), and libraries were tagmented, adaptor ligated, and indexed using the Nextera XT kit (Illumina). After normalization and pooling, libraries were sequenced on a Hiseq 4000 (Illumina) using paired-end 100bp reads. Raw sequencing files were demultiplexed with bcl2fastq, reads were aligned using STAR, the count matrix was generated using SummarizedExperiment, and differential expression analysis was performed using DESeq2 with standard settings.
Publication Title
CD22 blockade restores homeostatic microglial phagocytosis in ageing brains.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Clonal cellular variance often confounds reproducibility of forward and reverse genetic studies. We developed combinatorial approaches for whole genome saturated mutagenesis using haploid murine ES cells to permit induction and reversion of genetic mutations. Using these systems, we created a biobank with over 100000 individual ES cell lines with repairable and genetically bar coded mutations targeting 16950 genes. This biobank termed “Haplobank” is freely available. In addition, we developed a genetic color coding system for rapid repair of mutations and direct functional validation in sister clones. Using this system, we report functional validation of essential ES cell genes. We also identified phospholipase16G as a key pathway for cytotoxicity of human rhinoviruses, the most frequent cause of the common cold. Moreover, we derived 3D blood vessel organoids from haploid ES cells, combining conditional mutagenesis in haploid ES cells with tissue engineering. We identified multiple novel genes, such as Connexin43/Gja1, in blood vessel formation and tip cell specification in vitro and also in vivo. Taken together, we develop a conditional homozygous ES cell resource for the community to empower controlled genetic studies in murine ES cells and tissues derived from it. Overall design: RNA-Seq was carried out using standard protocols. https://www.haplobank.at/ecommerce/control/haplobank_resource
Publication Title
Comparative glycoproteomics of stem cells identifies new players in ricin toxicity.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 79 Downloadable Samples
- Illumina HiSeq 2500
Description
Introduction: A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. Aim: We have investigated how microRNAs contribute to core clock and clock-controlled gene expression using mice in which microRNA biogenesis can be inactivated in the liver. Results: While the hepatic core clock was surprisingly resilient to microRNA loss, whole transcriptome sequencing uncovered widespread effects on clock ouput gene expression. Cyclic transcription paired with microRNA-mediated regulation was thus identified as a widespread phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only a few mRNA rhythms were actually generated by microRNAs. Finally, we pinpoint several microRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to microRNA regulation. Conclusion: Our study provides a comprehensive analysis of miRNA activity in shaping hepatic circadian gene expression and can serve as a valuable resource for further investigations into the regulatory roles that miRNAs play in liver gene expression and physiology. Overall design: RNA-Seq of rRNA-depleted total RNAs from two independent full time series around-the-clock of Dicer knockout and control mouse livers
Publication Title
MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 82 Downloadable Samples
- Illumina HiSeq 2500
Description
BACKGROUND: The daily gene expression oscillations that underlie mammalian circadian rhythms show striking differences between tissues and involve post-transcriptional regulation. Both aspects remain poorly understood. We have used ribosome profiling to explore the contribution of translation efficiency to temporal gene expression in kidney, and contrasted our findings with liver data available from the same mice. RESULTS: Rhythmic translation of constantly abundant mRNAs affects largely nonoverlapping transcript sets with distinct phase clustering in the two organs. Moreover, tissue differences in translation efficiency modulate the timing and amount of protein biosynthesis from rhythmic mRNAs, consistent with organ-specificity in clock output gene repertoires and rhythmicity parameters. Our comprehensive datasets provided insights into translational control beyond temporal regulation. Between tissues, many transcripts show differences in translation efficiency, which are, however, of markedly smaller scale than mRNA abundance differences. Tissue-specific changes in translation efficiency are associated with specific transcript features and, intriguingly, globally counteracted and compensated transcript abundance variations, leading to higher similarity at the level of protein biosynthesis between both tissues. CONCLUSIONS: We show that tissue-specificity in rhythmic gene expression extends to the translatome and contributes to define the identities, the phases and the expression levels of rhythmic protein biosynthesis. Moreover, translational compensation of transcript abundance divergence leads to overall higher similarity at the level of protein production across organs. The unique resources provided through our study will serve to address fundamental questions of post-transcriptional control and differential gene expression in vivo. Overall design: A total of 48 mice were entrained under 12hours light:dark conditions for 2 weeks and also collected under 12hours light:dark. Mice were sacrificed every two hours during the 24 hours daily cycle. Two replicates per time point, each replicate is a pool of livers or kidneys from 2 animals.
Publication Title
Translational contributions to tissue specificity in rhythmic and constitutive gene expression.
Sample Metadata Fields
Sex, Cell line, Subject, Time
View Samples- Homo sapiens
- 38 Downloadable Samples
- IlluminaHiSeq2000
Description
Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by a family of adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. However, the role of A-to-I RNA editing in vascular disease is unknown. Here we show that cathepsin S mRNA (CTSS), which encodes a cysteine protease associated with angiogenesis and atherosclerosis, is highly edited in human endothelial cells. The 3' untranslated region (3' UTR) of the CTSS transcript contains two inverted repeats, the AluJo and AluSx+ regions, which form a long stem–loop structure that is recognized by ADAR1 as a substrate for editing. RNA editing enables the recruitment of the stabilizing RNA-binding protein human antigen R (HuR; encoded by ELAVL1) to the 3' UTR of the CTSS transcript, thereby controlling CTSS mRNA stability and expression. In endothelial cells, ADAR1 overexpression or treatment of cells with hypoxia or with the inflammatory cytokines interferon-? and tumor-necrosis-factor-a induces CTSS RNA editing and consequently increases cathepsin S expression. ADAR1 levels and the extent of CTSS RNA editing are associated with changes in cathepsin S levels in patients with atherosclerotic vascular diseases, including subclinical atherosclerosis, coronary artery disease, aortic aneurysms and advanced carotid atherosclerotic disease. These results reveal a previously unrecognized role of RNA editing in gene expression in human atherosclerotic vascular diseases. Overall design: 1) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in poly(A) RNA-seq data derived from endothelial cell transcriptome after ADAR1 or ADAR2 knockdown (n=2 biological replicates per condition, total n=8 biological samples). 2) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total-RNA-seq data derived from peripheral blood mononuclear cells (n=12 total biological samples; n=4 replicates per condition). 3) Evaluation of transcriptome expression and RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total-RNA-seq data derived from endothelial cell transcriptome under basal and hypoxic conditions (n=2 biological replicates per condition, total n=4 biological samples). 4) Evaluation of RNA editing sites (A-to-G and T-to-C nucleotide mismatches) in total RNA-seq data derived from endothelial cell transcriptome under basal and hypoxic conditions after ADAR1 knockdown (n=3 replicates per condition, total n=12 biological samples). 5) HuR iCLIP RNA-sequencing data derived from HUVEC HuR iCLIP after ADAR1 knockdown (scrambled control and siADAR1, n=1 per condition, total n=2 biological samples).
Publication Title
Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 348 Downloadable Samples
- Illumina HiSeq 2000
Description
Genetic variation governs protein expression through both transcriptional and post-transcriptional processes. To investigate this relationship, we combined a multiplexed, mass spectrometry-based method for protein quantification with an emerging mouse model harboring extensive genetic variation from 8 founder strains. We collected genome-wide mRNA and protein profiling measurements to link genetic variation to protein expression differences in livers from 192 Diversity Outcross mice. Overall design: Illumina 100bp single-end liver RNA-seq from 192 male and female Diversity Outbred 26-week old mice raised on standard chow or high fat diet. Each sample was sequenced in 2x technical replicates across multiple flowcells. Samples were randomly assigned lanes and multiplexed at 12-24x.
Publication Title
Epistatic Networks Jointly Influence Phenotypes Related to Metabolic Disease and Gene Expression in Diversity Outbred Mice.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 70 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared four transcription factor knockdowns using transgenic RNAi expressed in the larval fat body. FOXO, Tfb1, p53, and Stat92E-dependent gene expression in the Drosophila fat body was quantified on control and high-sugar diets in order to generate expression profiles via RNA-seq. These expression data were used to build a gene regulatory network to predict novel roles for these and other genes during caloric overload. Overall design: Control and fat body-expressed transcription factor RNAi Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M or 1M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples