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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- Oryza sativa
- 14 Downloadable Samples
Affymetrix Rice Genome Array (rice)
Description
Controversy regarding genetically modified (GM) plants and their potential impact on human health contrasts with the tacit acceptance
Publication Title
Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dynamic regulation of histone methylation by methyltransferases and demethylases plays a central role in regulating the fate of embryonic stem (ES) cells. The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene results in peri-implantation lethality and prevents the propagation of ES cells. However, Setdb1- null blastocysts do not display global changes in H3K9 methylation or DNA methylation, arguing against a genome- wide defect. Here we show that conditional deletion of the Setdb1 gene in ES cells results in the upregulation of lineage differentiation markers, especially trophectoderm-specific factors, similar to effects observed upon loss of Oct3/4 expression in ES cells. We demonstrate that KMT1E deficiency in ES cells leads to a decrease in histone H3K9 methylation at and derepression of trophoblast-associated genes such as Cdx2. Furthermore, we find genes that are derepressed upon Setdb1 deletion to overlap with known targets of polycomb mediated repression, suggesting that KMT1E mediated H3K9 methylation acts in concert with polycomb controlled H3K27 methylation. Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells.
Publication Title
KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 88 Downloadable Samples
- Illumina HiSeq 2500
Description
MYC is a potent oncogene associated with aggressive disease in many distinct tumor types. Transforming members of the MYC family (MYC, MYCL1, MYCN) encode transcription factors containing six highly conserved regions, termed MYC homology Boxes (MBs). Here, we conduct proteomic profiling of the MB interactomes, demonstrating that half of MYC interactors require one or more MBs for binding. Comprehensive phenotypic analyses revealed that two MBs are universally required for transformation. MBII interaction with acetyltransferase-containing complexes results in histone hyperacetylation and is essential for MYC-dependent tumor initiation. By contrast, MB0 interacts with transcription elongation factors through direct binding to the general transcription factor TFIIF, and deletion of MB0 severely inhibits tumor growth but is dispensable for tumor initiation. Notably, the full transforming activity of MYC can be restored upon co-expression of MB0 and MBII deletion mutants, indicating that these two regions confer unique biological functions, each required for oncogenic MYC activity. Overall design: RNA-seq analysis was conducted in TET21 cells (n=4, for each of the MYC deletion mutant ectopycally expressed) to determine the nature of the MB transcriptomes, and ChIPseq was conducted on WT-MYC TET21-expressing cells to determine MYC binding (n=1).
Publication Title
MYC Protein Interactome Profiling Reveals Functionally Distinct Regions that Cooperate to Drive Tumorigenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator (PRM). We now compare global endometrial gene expression in asoprisnil-treated versus control women and demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding.
Publication Title
Uterine NK cells regulate endometrial bleeding in women and are suppressed by the progesterone receptor modulator asoprisnil.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Human Umbilical Vein Endothelial Cells were treated with three newly synthesized compounds and DMSO as vehicle. Total RNA was isolated 6 and 24h after treatment and gene expression analysis was performed. Three independent experiments were performed, corresponding to rep1, rep2 and rep3. Experiment 1 (rep1) contained all substances at both time points tested. Experiment 2 (rep2) contained two of the compounds and control DMSO at both time points. Experiment 3 (rep3) contained the third compound and control DMSO at both time points.
Publication Title
Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis.
Sample Metadata Fields
Specimen part, Time
View Samples- 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
- 9 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However the difficulty in evaluating whether these candidate genes drive tumour progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumours with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumour progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, which can either promote individual or collective invasion, depending on the severity of effect on cohesin function.
Publication Title
A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of a NVS-ZP7-3 response signature in T-ALL cell lines to understand the transcriptional response in both Notch pathway active cell lines and Notch pathway inactive lines.
Publication Title
Discovery of a ZIP7 inhibitor from a Notch pathway screen.
Sample Metadata Fields
Cell line, Treatment
View Samples- Oryza sativa
- 12 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
We advance a three gene model of arsenate tolerance in rice based on testing root growth of 108 recombinant inbred lines (RILs) of the Bala x Azucena population. Marker genotype at 3 loci determined arsenate tolerance in 99% of RILs tested. Interestingly, plants must inherit 2, but any two alleles from the tolerant parent (Bala) to have the tolerant phenotype. Challenging the Affymetrix GeneChip Rice Genome array with Azucena and Bala RNA isolated from control and arsenate treated plants revealed 592 genes 2 fold-upregulated by arsenate and 696 downregulated. The array data was also used to identify which genes are expressed within the three target loci.
Publication Title
Rice-arsenate interactions in hydroponics: whole genome transcriptional analysis.
Sample Metadata Fields
No sample metadata fields
View Samples