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SRP055084
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Two secreted Toxoplasma proteins (GRA17 and GRA23) mediate the passage of small molecules between the host cytoplasm and the parasite-containing vacuole. This provides the first molecular explanation to how intracellular, vacuole-residing parasites in the phylum Apicomplexa, like Plasmodium, gain access to host nutrients. Methods: Mouse-derived Bone Marrow Macrophages were infected with Toxoplasma tachyzoites of either WT, dGRA17, dGRA23, or dGRA17rescue genetic background for 4 hours. Results: GRA23 gene expression levels are elevated in the dGRA17 strain but not vice versa. Conclusions: GRA17 and GRA23 are synergistically required for permeability of small molecules into the Toxoplasma parasitophorous vacuole. Overall design: Toxoplasma and Mouse gene expression profiles from BMDMs infected with either WT (control), dGRA17, gGRA23, or dGRA17rescue (control) tachyzoites were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at 4 hours post-infection.
Publication Title
The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome. Overall design: Examined transcriptome from U937 cells in biological triplicates.
Publication Title
The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain. Genetic deletion of ERK5 is embryonic lethal and tissue-restricted deletions have profound effects on erythroid development, cardiac function and neurogenesis. In addition, depletion of ERK5 is anti-inflammatory and anti-tumorigenic. Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology. Here we report the synthesis and biological characterization of potent, selective ERK5 inhibitors. In contrast to both genetic depletion/deletion of ERK5 and inhibition with previously reported compounds, inhibition of the kinase with the most selective of the new inhibitors had no anti-inflammatory or anti-proliferative activity. The source of efficacy in previously reported ERK5 inhibitors is shown to be off-target activity on bromodomains (BRDs), conserved protein modules involved in recognition of acetyl-lysine residues during transcriptional processes. It is likely that phenotypes reported from genetic deletion or depletion of ERK5 arise from removal of a non-catalytic function of ERK5. The newly reported inhibitors should be useful in determining which of the many reported phenotypes are due to kinase activity, and delineate which can be pharmacologically targeted. Overall design: Two cellular models with reported ERK5-regulated signaling were used: Pam3CSK4-stimulated HUVECs as a model of inflammation, and EGF-stimulated HeLa cells as an established cell model of ERK5 regulation. Cells were pre-incubated with DMSO vehicle, AX15836 (ERK5 inhibitor), AX15839 (dual ERK5/BRD inhibitor), or I-BET762 (BRD inhibitor), then stimulated with agonist. Cellular responses were verified by immunoassays and western blots using replicate wells in the same experiment.
Publication Title
ERK5 kinase activity is dispensable for cellular immune response and proliferation.
Sample Metadata Fields
Specimen part, Subject, Compound
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.
Publication Title
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- IlluminaHiSeq2000
Description
We recently identified ISRIB as a potent inhibitor of the integrated stress response (ISR). ISRIB renders cells resistant to the effects of eIF2a phosphorylation and enhances long-term memory in rodents (10.7554/eLife.00498). Here we show by genome-wide in vivo ribosome profiling that translation of a restricted subset of mRNAs is induced upon ISR activation. ISRIB substantially reversed the translational effects elicited by phosphorylation of eIF2a and induced no major changes in translation or mRNA levels in unstressed cells. eIF2a phosphorylation-induced stress granule (SG) formation was blocked by ISRIB. Strikingly, ISRIB addition to stressed cells with pre-formed SGs induced their rapid disassembly, liberating mRNAs into the actively translating pool. Restoration of mRNA translation and modulation of SG dynamics may be an effective treatment of neurodegenerative diseases characterized by eIF2a phosphorylation, SG formation and cognitive loss. Overall design: Ribosome profiling with paired RNA-seq
Publication Title
The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 5 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plant compensatory responses depends on transcriptional reprogramming. We used microarray analysis to understand the differential gene expression pattern between clipped (herbivore browsed)
Publication Title
Overcompensation in response to herbivory in Arabidopsis thaliana: the role of glucose-6-phosphate dehydrogenase and the oxidative pentose-phosphate pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina Genome Analyzer II
Description
To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta. Overall design: 3''-end Sequencing for Expression Quantification (3SEQ) and SNP Analysis to observe parent-of-origin bias in 28 placental samples at two time points and 2 yolk sac samples
Publication Title
Maternal bias and escape from X chromosome imprinting in the midgestation mouse placenta.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The goal of this study is to measure Arabidopsis mRNA transcription and mRNA decay rates genome wide at two temperatures, and thus to calculate the temperature coefficient of both processes. Sensing and response to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes to transcription or decay rates and whether passive or active temperature regulation is involved. Results Using a base analogue labelling method we directly measured the temperature coefficient (Q10) of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional mechanism process exists for the activethat controls of mRNA abundance by temperature/
Publication Title
Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study, using a Patient Derived Xenograft (PDX) system established by transplanting primary tumors from pre-metastatic breast cancer patients we demonstrate that development of distant organ metastases correlates with the presence of Bone Marrow Disseminated Tumor Cells (BM DTCs) in the PDX mice. Comparative gene expression analysis of bone marrow (BM) from tumor bearing PDX mice which developed metastatic disease was carried out with BM from non-tumor bearing controls.
Publication Title
Identifying biomarkers of breast cancer micrometastatic disease in bone marrow using a patient-derived xenograft mouse model.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
mRNA expression in the spinal cords of the G93A-SOD1 familial ALS transgenic mouse model was compared to that in nontransgenic (Normal mouse) and transgenic mice expressing wild-type (WT)SOD1. Gene Ontology (GO)analysis was used to characterize differences in expression between G93A-SOD1 mouse and nontransgenic mouse spinal cord. Changes in multiple GO categories were found. Many of these were associated with subsystems involving cell-cell communication and intracellular signal transduction. Expression profiles of mice expressing WT-SOD1 did not differ from nontransgenic mice. In contrast, protein profiling using proteomics technology indicated changes in mitochondrial protein expression in the G93A-SOD1 mouse spinal cord that were not found in the mRNA expression analysis.
Publication Title
Informatics-assisted protein profiling in a transgenic mouse model of amyotrophic lateral sclerosis.
Sample Metadata Fields
Age
View Samples