We used microarrays to detail the global programme of gene expression after knockdown of Ecdysoneless in hMECs
The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells.
Specimen part, Cell line
View SamplesAda3 (alteration/deficiency in activation) is a transcriptional adaptor that forms a core structural component of multiple HAT complexes. In order to gain insights into physiological roles of Ada3, we made a conditional knockout mouse for Ada3 which was early embryonic lethal. Deletion of Ada3 in MEFs by using Adenovirus-Cre showed changes in global histone acetylation.
Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.
Specimen part
View SamplesGene expression of mouse hepatoblasts (HBs) expressing IDH1 WT, IDH1 R132C, IDH2 WT, R172K and empty vector controls (N=2 cultures for each condition) grown on collagen-coated plates and IDH1 R132C and empty vector controls on uncoated plates were evaluated using Affymetrix Mouse 430Av2 DNA microarrays that were processed at the Dana-Farber Cancer Institute core facility (http://macf-web.dfci.harvard.edu/) using their standard protocol.
Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer.
Specimen part
View SamplesMutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-Hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2- hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D2-HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life spanrecapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant upregulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2R140Q expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2R140Q in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.
Specimen part
View SamplesWildtype B6, Rag1-/- B6 and Rag1-/- B6 mice harboring the 225.4 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron
IgA response to symbiotic bacteria as a mediator of gut homeostasis.
No sample metadata fields
View SamplesResearch conducted using the novel approach of Next Generation Sequencing to determine the differentially expressed microRNAs in whole blood samples from prostate cancer patients. Overall design: The whole blood miRNA samples from both controls and patients were sequences and a differential expressional analysis was conducted to identify possible biomarkers to distinguish patients from controls.
A Panel of MicroRNAs as Diagnostic Biomarkers for the Identification of Prostate Cancer.
Specimen part, Disease stage, Subject
View SamplesIMP3 (IGF2-mRNA binding protein 3) is a member of a family of IGF2-mRNA binding proteins that function in RNA stabilization, trafficking and localization. It exhibits the properties of an oncofetal protein and its expression correlates with the aggressive behavior of many tumors. In breast cancer, IMP3 is associated with the highly aggressive triple-negative subtype (TNBC) The challenge is to identify specific proteins and functions that are regulated by IMP3. As an approach to this problem, we compared the mRNA expression profile of SUM-1315 cells, a TNBC cell line, to the same cells that had been depleted of IMP3. Overall design: SUM-1315 breast cancer cells were were infected with lentivirus for control shRNA and two different IMP3 shRNAs and processed for RNA-sequencing
IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer.
Specimen part, Subject
View SamplesBackgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Age, Specimen part, Treatment
View SamplesHelicobacter pylori infection is associated with development of gastric adenocarcinoma in a subset of infected humans, especially those that develop an antecedent condition, chronic atrophic gastritis (ChAG) characterized by loss of acid-producing parietal cells. Studies in a gnotobiotic transgenic mouse model of ChAG, with an engineered ablation of parietal cells and an associated expansion of gastric epithelial progenitors (GEPs), have shown that a subset of GEPs is able to harbor intracellular collections of H. pylori. To better understand H. pyloris adaptation to ChAG, we sequenced the genomes of 24 isolates, obtained from 6 individuals, each sampled over a 4-year interval, as they maintained normal gastric histology, or progressed from normal histology to ChAG, or experienced worsening ChAG, or proceeded from ChAG to cancer. Analyses of gene content and single nucleotide polymorphisms (SNPs) demonstrated that H. pylori populations within study participants were largely clonal, and remarkably stable over the 4-year interval, regardless of disease state. Because they exhibited such broad inter-host variation (38.64.7 SNPs/1000bp of genome), and did not cluster according to host pathology, we sought to identify common functional properties by performing GeneChip studies of the responses of a cultured mouse gastric stem cell-like line (mGEPs) to infection with sequenced strains. The results yielded a shared 695-member set of genes differentially expressed after infection with ChAG-associated, but not normal or heat killed strains: 434 of these genes were also represented in dataset of responses to the cancer-associated strain. Ingenuity Pathway Analysis revealed that ChAG- and ChAG/cancer- associated responses were significantly enriched in genes associated with tumorigenesis in general, and gastric carcinogenesis in specific cases. Whole genome transcriptional profiling of a sequenced ChAG strain during mGEP infection disclosed a set of responses that included upregulation of hopZ, an adhesin belonging to a family of outer membrane proteins. Expression profiles of wild-type and hopZ strains revealed a number of pH-regulated genes affected by loss of HopZ, including HopP which binds sialylated glycans produced by GEPs in vivo. Genetic inactivation of hopZ produces a fitness defect in gnotobiotic transgenic mice but not their wild-type littermates. This study illustrates an approach for identifying GEP responses specific to ChAG, and bacterial genes important for survival in a gastric ecosystem that lacks parietal cells.
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Age, Specimen part, Treatment
View Samples