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SRP113494
Mus musculus
142 Downloadable Samples
Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX), however the differentially translating mRNAs that contribute to altered neural function are not known. We used Translating Ribosome Affinity Purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1-/y) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded. Surprisingly, enhancement rather than inhibition of M4 activity normalizes core phenotypes in the Fmr1-/y, including excessive protein synthesis, exaggerated mGluR-LTD, and audiogenic seizures. These results suggest that not all excessively translated mRNAs in the Fmr1-/y brain are detrimental, and some may be candidates for enhancement to correct pathological changes in the FX brain. Overall design: 6 biological replicates of total hippocampal mRNA (Input) from WT and Fmr1 KO littermate pairs and CA1-TRAP-IP (IP) from the same 6 WT and KO littermate pairs.
Publication Title
Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Promoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of tumour suppressor inactivation in cancer, including malignant brain tumours.
Publication Title
Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Sus scrofa
- 83 Downloadable Samples
- Illumina HiSeq 2000
Description
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of 3rd trimester pregnant pigs can result in transmission of the virus to the fetus and ultimately death in utero or postnatally. Little is known about the immune response to infection at the maternal-fetal interface and in the fetus itself, or the molecular events behind virus transmission and disease progression in the fetus. To investigate these processes, RNA-sequencing of two tissues, uterine endothelium adjacent to the umbilical attachment site and fetal thymus, was performed 21 days post challenge on four groups of fetuses selected from a large PRRSV challenge experiment of pregnant gilts. Overall design: RNA-seq experiment compared gene expression between four different groups of fetuses (n=12 per group): control (CON-uninfected fetuses from mock inoculated gilts), UNINF (uninfected fetuses from PRRSV-inoculated gilts), INF (infected fetuses from PRRSV-inoculated gilts), and meconium-stained fetuses (MEC-meconium-stained fetuses from PRRSV-inoculated gilts) and investigated two tissues: uterine endometrium (with adherent placental tissue) at the site of umbilical attachment and fetal thymus (96 samples in total). Three contrasts were performed for the differential expression (edgeR) and network (WGCNA) analyses: UNINF v CON, INF v UNINF, and MEC v INF.
Publication Title
Genome-wide analysis of the transcriptional response to porcine reproductive and respiratory syndrome virus infection at the maternal/fetal interface and in the fetus.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Nonsense-mediated RNA decay (NMD) is regulated by a variety of cellular stresses. We expose U2OS cells to several stresses and assess RNA expression in the absence of transcription (i.e. stability). These studies identify transcripts that are stabilized by the physiological inhibition of NMD.
Publication Title
Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Effect of the ablation of connexin 30 in the stria vascularis
Publication Title
Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis.
Sample Metadata Fields
Age, Specimen part, Disease, Time
View Samples- Rattus norvegicus
- 56 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
We profiled hepatic transcriptional responses of 6 strains of rats with varying sensitivity to a dioxin, TCDD, at 19 hours following exposure. The resistant rats exhibited significantly reduced transcriptional responses in comparison to the sensitive strains. We hypothesize that genes which show differential changes between the resistant and sensitive rats may potentially explain sensitivity.
Publication Title
Inter-strain heterogeneity in rat hepatic transcriptomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The oncogenic proteins expressed in human cancer cells are exceedingly difficult targets for drug discovery due to intrinsic properties of the Ras GTPase switch. As a result, recent efforts have largely focused on inhibiting Ras-regulated kinase effector cascades, particularly the Raf/MEK/ERK and PI3 kinase/Akt/mTOR pathways. We constructed murine stem cell leukemia virus (MSCV) vectors encoding oncogenic K-RasD12 with additional second site amino acid substitutions that that impair PI3 kinase/Akt or Raf/MEK/ERK activation and performed bone marrow transduction/transplantation experiments in mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins induced aggressive clonal T lineage acute lymphoblastic leukemia (T-ALL). These leukemias exhibited a high frequency of somatic Notch1 mutations, which is also true of human T-ALL. Multiple independent T-ALLs restored full oncogenic Ras activity by acquiring third site mutations within the viral KrasD12 transgenes. Other leukemias with undetectable PTEN and elevated phosphoryated Akt levels showed a similar gene expression profile to human early T progenitor (ETP) T-ALL. Expressing oncoproteins that are defective for specific functions is a general strategy for assessing requirements for tumor maintenance and uncovering potential mechanisms of drug resistance in vivo. In addition, our observation that defective Kras oncogenes regain potent cancer initiating activity strongly supports simultaneously targeting distinct components of Ras signaling networks in the substantial fraction of cancers with RAS mutations.
Publication Title
Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 3000
Description
We recently reported that single-cell derived isogenic subclones of SKMEL5 cells have differential initial sensitivity to BRAF-inhibitors. In order to probe differences among these subclones, we selected three subclones with unique drug responses: progressing (SK-MEL-5 SC10), stationary (SK-MEL-5 SC07), and regressing (SK-MEL-5 SC01) and performed RNASeq. This study examines differentially expressed genes (DEGs) among the subclones to identify the molecular basis for initial differences in drug sensitivity. Overall design: Transcriptomics analysis between single-cell derived isogenic subclones of BRAF-mutated melanoma cell line, SK-MEL-5
Publication Title
A Nonquiescent "Idling" Population State in Drug-Treated, BRAF-Mutated Melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Expression profiling of mRNA abundance in the adult mouse olfactory epithelium during replacement of OSNs forced by the bilateral ablation of the olfactory bulbs. The experiment was done on 6 week old male C57Bl/6 mice. Olfactory epithelium tissue samples were collected on days 1, 5, and 7 after bulbectomy. The cellular processes activated by bulbectomy include apoptosis of mature olfactory sensory neurons, infiltration of macrophages and dendritic cells, stimulation of proliferation of basal cell progenitors, and differentation of new sensory neurons.
Publication Title
Transcriptional changes during neuronal death and replacement in the olfactory epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis.
Publication Title
Two phases of disulfide bond formation have differing requirements for oxygen.
Sample Metadata Fields
Treatment
View Samples