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GSE79508
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic and degenerative disease in humans. Here, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B downregulated mTOR activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via the transcription factor TFEB, which increased lysosomal biogenesis and activation of autophagy-initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome population and basic recycling functions in the cell.
Publication Title
Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype. Organoid cells derived from mouse livers under various conditions, wild-type, Yap ON (Plus Dox), and Yap ON then OFF (Minus Dox) was examined.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype.
Publication Title
Hippo pathway activity influences liver cell fate.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Wildtype B6, Rag1-/- B6 and Rag1-/- B6 mice harboring the 225.4 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron
Publication Title
IgA response to symbiotic bacteria as a mediator of gut homeostasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 37 Downloadable Samples
Illumina HiSeq 2000
Description
Research 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.
Publication Title
A Panel of MicroRNAs as Diagnostic Biomarkers for the Identification of Prostate Cancer.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
IMP3 (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
Publication Title
IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
Backgropund: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.
Publication Title
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Helicobacter pylori
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Helicobacter 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.
Publication Title
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples