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GSE134114
Homo sapiens
11 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Intrahepatic Cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. Recently, aberrant Notch signaling was reported in iCCA carcinogenesis. Specifically, altered expression and/or activation of the receptors Notch1/2 suggests a role for Notch pathway overactivation during iCCA formation and progression. In this study, we examined the effects of Notch inhibition by γ-secretase inhibitor, LY3039478 in human iCCA cell lines and in an excellent patient derived-xenograft (PDX) model. Expression of several Notch pathway components, including NICD, Hes1, and DLL4, were reduced after GSI treatment. Moreover, LY3039478 inhibits cell migration and invasion while in GSI-treated mice, tumor growth was delayed compared to vehicle and chemotherapy. These results support the notion that Notch inhibition by GSI may reduce in vivo tumorigenesis. In addition, GSI reduces in PDX model VEGFA and MMP13 involved in capillary tube formation and tumor progression. Here, we therefore show a link between the efficacy of Notch inhibition and the tumor microenvironment through LY3039478 that slows tumor progression compared to control mice blocking angiogenesis via MMP13 downregulation.
Publication Title
Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify the genes and pathways regulated by FOXF2, we investigated potential FOXF2 gene targets by microarray analyses of primary prostate stromal cells (PrSC) in which FOXF2 was knocked down by siRNA. 190 differentially expressed genes were selected, of which 104 genes were more highly expressed in PrSC cells treated with FOXF2 siRNA and 86 were more highly expressed in PRSC cells treated with negative control siRNA.
Publication Title
The FOXF2 pathway in the human prostate stroma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Long non-coding RNAs show highly tissue and disease specific expression profiles. We analyzed prostate cancer and normal adjacent prostate samples to identify cancer-specific transcripts and found 334 candidates, of which 15 were validated by RT-PCR.
Publication Title
Novel long non-coding RNAs are specific diagnostic and prognostic markers for prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
RhoGDIbeta (ARHGDIB) is often expressed in tumor cells. It negatively regulates Rho-GTPases, but may have other functions as well. To analyze its effect on gene expression, RhoGDIbeta was suppressed by RNA interference in MDA-MB-231 breast cancer cells and changes in gene expression monitored by cDNA microarrays.
Publication Title
Cyclooxygenase-2 is a target gene of rho GDP dissociation inhibitor beta in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 74 Downloadable Samples
Illumina HiSeq 2000
Description
Ubiquitous expression of ALS-causing mutations in superoxide dismutase 1 (SOD1) provoke non-cell autonomous paralytic disease. By combining ribosome affinity purification and high-throughput sequencing, a cascade of mutant SOD1-dependent, cell type-specific changes are now identified. Initial mutant-dependent damage is restricted to motor neurons and includes synapse and metabolic abnormalities, endoplasmic reticulum (ER) stress, and selective activation of the PERK arm of the unfolded protein response. PERK activation correlates with what we identify to be a naturally low level of ER chaperones in motor neurons. Early changes in astrocytes are to genes involved in inflammation and metabolism and that are targets of the PPAR and LXR transcription factors. Dysregulation of myelination and lipid signaling pathways and activation of ETS transcription factors occur in oligodendrocytes only after disease initiation. Thus, pathogenesis involves a temporal cascade of cell type selective damage initiating in motor neurons, with subsequent damage within glia driving disease propagation. Overall design: Cell type-specific mRNA was purified by ribosome affinity purification from the spinal cord of bacTRAP reporter mice that label selective cell types by EGFP-tagged ribosome RPL10A. Sequencing libraries were prepared from 3-6 biological replicates for each genotype to determine the mutant induced gene expression changes in specific cell types.
Publication Title
Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS.
Sample Metadata Fields
Sex, Specimen part, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
One goal of viral infection is to reprogram the host cell to optimize viral replication. As part of this process, viral miRNAs may compete for components of the miRNA/siRNA pathway as well as regulate cellular targets. Mouse Cytomegalovirus has been described to generate large numbers of viral miRNAs during lytic infection and was therefore used to analyze the impact of viral miRNAs on the host cell small RNA system as well as to check for sorting of viral small RNAs into specific Ago-proteins. Deep sequencing analysis of MCMV infected cells revealed that viral miRNAs represent only app. 13% of all detected miRNAs. All previously described MCMV miRNAs with the exception of miR-m88-1* were confirmed and for the MCMV miR-m01-1 hairpin an additional miRNA, designated miR-m01-1-3p, was found. Its presence was confirmed by qPCR and Northern Blot. Deep sequencing after RISC IP with antibodies specific for either Ago1 or Ago2 showed that all MCMV miRNAs are loaded into both RISC complexes. The ratio of MCMV to mouse miRNAs was not increased after immunoprecipitation of Ago-proteins. Viral miRNAs therefore do not overwhelm the host miRNA processing system nor are they preferentially incorporated into RISC. We found that 3 mouse miRNAs showed an altered expression due to MCMV infection. Down-regulation of miR-27a, as previously described, could be confirmed. In addition, miR-26a was down-regulated and an up-regulation of miR-7a dependent on viral protein expression could be observed. Overall design: Examination of small RNA expression in uninfected vs. infected cells, immunoprecipitation + sequencing of Ago1 and Ago2 loaded small RNAs in infected cells
Publication Title
Murine cytomegalovirus infection of cultured mouse cells induces expression of miR-7a.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Temporally restricted feeding is known to impact the circadian clock. This dataset shows the effects of temporally restricted feeding on the hepatic transcriptome.
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Restricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Immunoprecipitation of EGFR from irradiated A549 (ATCC CCL185) cells was performed in order to characterize bound mRNA species with the help of microarray analysis
Publication Title
New roles for nuclear EGFR in regulating the stability and translation of mRNAs associated with VEGF signaling.
Sample Metadata Fields
Cell line, Treatment
View Samples