Filters
Technology
Platform
SRP090169
Mus musculus
18 Downloadable Samples
Illumina HiSeq 2000
Description
The molecular chaperone heat shock protein 90 (HSP90) is thought to buffer genetic variation uncoupling phenotypic outcome from individual genotypes. HSP90 thus acts as an evolutionary capacitor by facilitating an accumulation of natural genetic variation. The molecular mechanism underlying the buffering ability is unclear, and HSP90-contingent genetic variation maps both to coding and non-coding parts of the genome. Our genome-wide data indicate that a compromised chaperoning activity of HSP90 causes derepression of endogenous retroviruses (ERVs) in mouse somatic cells. This results in an upregulation of host genes located in the neighborhood of pre-existing ERVs insertion sites. We provide genetic and biochemical evidence that HSP90 cooperates with KAP1/ SETDB1 histone methyltranferase pathway to repress ERVs. Individual mouse strains have unique integration sites of ERVs in their genomes. Consequently distinct genes are responsive to HSP90 inhibitor in different mouse strains depending on the position of the genes vis-Ã -vis strain-specific ERV insertion sites. Since ERVs have been exapted to drive novel transcriptional networks during mammalian evolution, HSP90 may have acted as a capacitor by buffering variation caused by ERV in non-coding regions of the genome. Our studies provide the first molecular framework by which HSP90 can mitigate genetic variation in gene-regulatory regions affecting gene expression and phenotypes. Overall design: We have performed RNA-seq in mouse embryonic stem cells, neuronal progenitor cells and bone-marrow-derived macrophages treated with NVP-AUY922 in triplicates.
Publication Title
The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 1500
Description
Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2. We identified that compared to other flame retardants, TCEP and TCIPP had little cytotoxicity. Treatment with sub-cytotoxic concentrations of the two compounds revealed that both chemicals elicited similar effects; both compounds were found to affect genes involved in immune responses and steroid hormone biosynthesis, while also affecting xenobiotic metabolism pathways in a similar manner. Specifically for effects on immune responses, both compounds were shown to alter the expression of the receptor of the potent and pleiotropic complement component, C5a. Additionally, expression of genes encoding for effector proteins involved in the complement cascade along with other potent inflammatory regulators were found altered in response to TCEP and TCIPP, further emphasizing their potential effects on immune function. Taken together, given that TCIPP elicited similar effects compared to TCEP, and at lower concentrations, the potential health effects of TCIPP need to be further studied for a complete risk assessment of the compound. Overall design: HepG2 cells were treated with low (25 uM) or high (250 uM) concentrations of tris(2-chloroethyl) phosphate (TCEP), low (2.5 uM) or high (25 uM) concentrations of tris(2-chloroisopropyl) phosphate (TCIPP). For control purposes, cells were exposed to 0.1% DMSO alone. Treatment lasted for 72 hours. Treatments were done in triplicate for each condition involving separate cell seeding, cell growth, treatments and RNA extractions per triplicate. RNA was isolated with Trizol (Invitrogen, USA) and RNeasy Kit (Qiagen, GER). Libraries were prepared with the TruSeq Stranded mRNA Sample Preparation Kit (Illumina, USA). 50bp long paired-ends reads were sequenced using the HiSeq(R) 1500 platform (Illumina, USA). Alignment, mapping and annotation of sequenced reads were performed using the CLC Genomics Workbench (CLC Bio, Aarhus, Denmark). Samples were normalized by quantile normalization before being mapped and annotated using the human reference hg19 genome.
Publication Title
A toxicogenomics approach to screen chlorinated flame retardants tris(2-chloroethyl) phosphate and tris(2-chloroisopropyl) phosphate for potential health effects.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 1500
Description
Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels. Over-representation and gene set enrichment analysis corresponded well and revealed that TBOEP treatments resulted in an upregulation of genes involved in protein and energy metabolism, along with DNA replication. Such increases in cell and macromolecule metabolism could explain the increase in mitochondrial activity at lower TBOEP concentrations. In addition, TBOEP affected a wide variety of biological processes, the most notable one being the general stress response, wound healing. Finally, TBOEP showed effects on steroid hormone biosynthesis and activation, regulation, and potentiation of immune responses, in agreement with other studies. As such, this study is the first study investigating genome-wide changes in gene transcription in response to TBOEP in human cells. Overall design: HepG2 cells were treated with low (2.5 uM) or high (125 uM) concentrations of Tris (2-butoxyethyl) phosphate (TBOEP) in 0.1% DMSO. For control purposes cells were exposed to 0.1% DMSO alone. Treatment lasted for 72 hours. All treatments were conducted in triplicates, involving separate seeding of cells. RNA was isolated with Trizol (Invitrogen, USA) and RNeasy Kit (Qiagen, GER). Libraries were prepared with the TruSeq Stranded mRNA Sample Preparation Kit (Illumina, USA). 50bp long paired-ends reads were sequenced using the HiSeq(R) 1500 platform (Illumina, USA). Alignement to the UCSC hg19 assembly of the human genome, mapping and annotation was performed with CLC Genomics Workbench (CLC Bio, DEN). Samples were normalised by quantile normalisation. Differential expression p-values were generated using Baggerly''s test statistic. These p-values were subsequently corrected with the Benjamini-Hochberg procedure to limit the false discovery rate (FDR) to 5% of the significant genes .
Publication Title
Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2 cells using RNA-seq.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Filtered selection coupled with support vector machines generate functionally relevant prediction model for colorectal cancer. In this study, we built a model that uses Support Vector Machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300 and 500 genes most relevant to CRC using the Minimum-RedundancyMaximum-Relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function and sigmoid).
Publication Title
Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
To identify genes regulated by BRD4 and to provide insight into new mechanisms de-regulated by BRD4, such as the response to oxidative stress, we integrated BRD4-binding regions with BRD4 gene expression data. For this analysis we performed BRD4 chromatin immunoprecipitation experiments and BRD4 knock down experiments followed by RNA-Seq analyses. By integration of both gene lists we identified top candidate genes regulated by BRD4. Overall design: HEK cells have been investigated for genomewide BRD4 binding sites and expression changes after knock down of BRD4. Illumina sequencing was used to gather data of the type ChIP Seq and mRNA Seq.
Publication Title
The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Publication Title
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 239 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Publication Title
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Timed sleep restriction designed to mimic human shift work was performed over a 2 week period in mice. On the final day, tissues were collected at 6 hour intervals to exmaine the effects of sleep restriction on circadian gene expression.
Publication Title
Circadian desynchrony promotes metabolic disruption in a mouse model of shiftwork.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The molecular mechanisms by which individuals subjected to environmental heat stress either adapt or develop heat-related complications are not well understood. We analysed the changes in blood mononuclear gene expression patterns in human volunteers exposed to an extreme heat in a sauna (temperature of 78 6 C).
Publication Title
A Model of Exposure to Extreme Environmental Heat Uncovers the Human Transcriptome to Heat Stress.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Mature B cells leave the bone marrow as naïve B cells and migrate to the secondary lymphoid organs where they encounter the antigen for the first time. This interaction stimulates B cells to rapidly grow and form characteristic histological structures called germinal center. In the germinal centers, B cells are targeted by mechanisms of genetic editing of the immunoglobulin loci, namely somatic hypermutation and class switch recombination, undergo selection for high affinity immunoglobulin receptors and are committed to differentiate into memory B cells or plasma cells. GCs display two histological areas the dark and the light zone that have been characterized as functionally distinct compartments through which B cells recycle multiple times during the germinal center reaction. Overall design: Naïve, germinal center and memory B cells were isolated from three independent donors each.
Publication Title
MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples