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GSE50541
Homo sapiens
28 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human adenovirus 5 encodes a small set of miRNAs, which are generated by DICER-mediated processing of 2 larger precursors, the so-called virus-associated RNAs I and II. To identify targets of one of the major miRNA isoforms derived from virus-associated RNAI (mivaRNAI-137), we isolated Argonaute complexes of mivaRNAI-137-transfected cells and analyzed co-purifying RNAs by microarray analysis. RNAs enriched in Argonaute complexes of mivaRNAI-137-transfected cells compared to cells transfected with a control siRNA were identified and subjected to further validation. RNAs specifically associated with Argonaute-containining complexes of adenovirus 5-infected cells were identified as well.
Publication Title
Identification of RISC-associated adenoviral microRNAs, a subset of their direct targets, and global changes in the targetome upon lytic adenovirus 5 infection.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced 3D phenotypic high-content assay and screened a library of FDA/EMA approved small molecules for inhibiting ECM deposition. Fibrotic Pattern Detection by Artificial Intelligence (FANTAIL) identified Tranilast as an effective inhibitor, however, by structure-activity relationship studies we found N-(2-butoxyphenyl)-3-(phenyl)acrylamides (N23Ps) as a novel and highly potent compound class. N23Ps suppressed myofibroblast transdifferentiation, ECM deposition, cellular contractility, and altered cell shapes, thus advocating a unique mode of action. Mechanistically, transcriptomics identified SMAD (de)ubiquitination/Smurf2 as a potential therapeutic target network. Antifibrotic activity of N23Ps was verified by proteomics in a human ex vivo tissue fibrosis disease model, suppressing profibrotic markers SERPINE1/PAI1 and CXCL8/IL8. Conclusively, these data suggest N23Ps as a novel class of highly potent compounds with implications for inhibiting organ fibrosis in patients.
Publication Title
Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MiR-221 overexpression leads to activation of apoptosis, growth arrest and reduced invasivness in PCa cells. Interaction of miR-221 with potential target genes was analyzed by a genome wide expression profiling.. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real Time RT-PCR assay (IRF1, IRF2 SOCS3, STAT1), and Western Blotting. In total, 282 genes were upregulated and 64 downregulated based on a more than 2-fold difference to untransfected PC-3 cells. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, tumorigenesis and inflammation. We confirmed dysregulation of IRF-2 SOCS3, STAT1,IRF9. These results indicate that miR-221 overexpression might lead to activation of the JAK/STAT pathway and downregulation of miR-221 might contribute to tumorigenesis in PCa cells.
Publication Title
Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Menisci play a vital role in load transmission, shock absorption and joint stability. The current dogma is that the menisci simply protects the cartilage and play no role in osteoarthritis (OA) unless they are injured. However, there is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, 2) to examine gene expression in OA meniscal cells compared to normal control meniscal cells, and 3) to test the hypothesis that OA meniscal cells are different from normal meniscal cells.
Publication Title
Analysis of meniscal degeneration and meniscal gene expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Neuronal function critically depends on coordinated subcellular distribution of mRNAs. Disturbed mRNA processing and axonal transport has been found in spinal muscular atrophy and could be causative for dysfunction and degeneration of motoneurons. Despite the advances made in characterizing the transport mechanisms of several axonal mRNAs, an unbiased approach to identify the axonal repertoire of mRNAs in healthy and degenerating motoneurons has been lacking. Here we used compartmentalized microfluidic chambers to investigate the somatodendritic and axonal mRNA content of cultured motoneurons by microarray analysis. In axons, transcripts related to protein synthesis and energy production were enriched relative to the somatodendritic compartment. Knockdown of Smn, the protein deficient in spinal muscular atrophy, produced a large number of transcript alterations in both compartments. Transcripts related to immune functions, including MHC class I genes, and with roles in RNA splicing were upregulated in the somatodendritic compartment. On the axonal side, transcripts associated with axon growth and synaptic activity were downregulated. These alterations provide evidence that subcellular localization of transcripts with axonal functions as well as regulation of specific transcripts with nonautonomous functions is disturbed in Smn-deficient motoneurons, most likely contributing to the pathophysiology of spinal muscular atrophy.
Publication Title
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4. Overall design: ES cells and cardiomyocytes with Hey1 or Hey2 overexpression were compared to control cells
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Early onset sepsis due to Group B streptococcus (GBS) leads to neonatal morbidity, increased mortality and long term neurological deficencies. Interaction between septicemic GBS and confluent monlayers of human coronary artery endothelial cells (HCAEC) was analyzed by a genome wide expression profiling. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real Time RT-PCR assay (Granulocyte chemotactic protein 2 (CXCL6)), ELISA (Urokinase, Cyclooxygenase 2 (COX2), Granulocyte chemotactic protein 1 (IL8)) and Western Blotting (Heme oxygenase1, BCL2 interacting protein (BIM)) at various time points between 4 and 24 hours. In total, 124 genes were differentially regulated (89 upregulated, 35 downregulated) based on a more than 3-fold difference to unstimulated HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection and inflammation. We confirmed upregulation of urokinase (UPA), COX2, HMOX1 and BCL2 interacting protein and downregulation of CXCL6 and IL8. These results indicate that GBS infection might lead to impaired function of the innate immune system and might contribute to hemorrhagic and inflammatory complications during GBS sepsis.
Publication Title
Infection of human coronary artery endothelial cells by group B streptococcus contributes to dysregulation of apoptosis, hemostasis, and innate immune responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Using measles virus induced T cell suppression as a model, we established that T cell inhibitory protein isoforms can be produced from alternatively spliced pre-mRNAs as a result of virus-mediated ablation of T cell receptor dependent activation of the phosphatidylinositol-3-kinase (PI3K). To asses production of alternative splice variants in response to PI3K abrogation in T cells at a whole cell level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) on T cell suppression. Applying our algorithm on this model 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulated at the level of AS or RG were found enriched in different functional groups with AS targeting e. g. extra cellular matrix (ECM)-receptor interaction and focal adhesion, while cytokine-receptor interaction, Jak-STAT and p53 pathways were mainly RG. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry strongly supporting the notion that PI3K abrogations interferes with key T cell activation processes at both levels, and that candidates represented within both categories bear the potential to actively contribute to T cell suppression
Publication Title
Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples