The absence of the Rb tumor suppressor gene changes levels/activities of transcription factors (e.g., E2F and p53) which alter gene expression patterns, related to cell cycle control and cellular response to DNA damage. Cisplatin is a genotoxic chemotherapeutic agent and wildtype or Rb null cells have different sensitivities to cisplatin-induced cytotoxicity.
Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma-deficient cells to DNA damage-induced necrosis.
No sample metadata fields
View SamplesFetal spleens were collected at days 82 and 97 of gestation following maternal infection with BVDV on day 75 of gestation.
Attenuated lymphocyte activation leads to the development of immunotolerance in bovine fetuses persistently infected with bovine viral diarrhea virus†.
Sex, Specimen part
View SamplesMicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function. Overall design: Three RNA samples containing bilateral entire hippocampi from three different mice, per group. Group 1 were injected with vector containing GFP and a miR34sp/miR9sp and the other group were subjected to a vector expressing GFP only.
Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.
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View SamplesAffymetric arrays were performed on thyroid samples collected from GEMMs: normal thyroid, TPO-Cre/LSL-Braf (PTC), TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (ATC) and TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (recurrent tumors)
Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers.
Specimen part
View SamplesWe characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.
Transcriptional ontogeny of the developing liver.
Specimen part
View SamplesWe established a neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high throughput sequencing (AGO2-RIP-seq) to analyse the regulatory role of miRNAs in mouse hippocampal neurons. Using this technique, we identified more than two thousand miRNA target genes in hippocampal neurons, regulating essential neuronal features such as axon guidance and transcription. Furthermore, we found that stable inhibition of the highly expressed miR-124 in hippocampal neurons led to significant changes in the AGO2 binding of target mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. Our data suggest that target redundancies are common among microRNA families. Together, these findings greatly enhance our understanding of the mechanisms and dynamics through which miRNAs regulate their target genes in neurons. Overall design: Analysis of the miRNA targetome in hippocampal neurons after inhibition of 2 different miRNAs. AAV5 injections into the hippocampus of adult C57BL/6 mice producing either of the following under a synapsin promoter: GFP only (Samples beginning with ''GFP124…'' or ''GFP125…''), GFP-miR124sp (Samples beginning with ''miR124…''), GFP-miR125sp (Samples beginning with ''miR125…''), GFP-AGO2-miR292sponge (samples ending with ''…292''), GFP-AGO2-miR124sponge (samples ending with ''…124''), GFP-AGO2-miR125sponge (samples ending with ''…125''). All other samples were sham-injected.
Identification of the miRNA targetome in hippocampal neurons using RIP-seq.
No sample metadata fields
View SamplesPurpose: To identify genes that are transcriptionally controlled by Notch signaling during zebrafish lateral line proneuromast formation. Methods: We isolated primordium cells from dissected tails of 36 hpf Tg((cldnB:GFP);Tg(cldnB:gal4) x Tg(UAS:nicd)) and sibling Tg((cldnB:GFP);Tg(cldnB:gal4)) embryos by FACS and performed RNASeq analysis. Results: Using an optimized data analysis workflow, we mapped about 26 million sequence reads per sample to the zebrafish genome (build danRer10) and identified 32,105 transcripts in the dissociated tails of WT and NICD zebrafish with TopHat workflow. Approximately 2% of the transcripts showed differential expression between the WT and NICD tails, with a fold change =0.5 and p value <0.01. Conclusion: RNASeq analyses revealed that Notch signaling cell-autonomously induces apical constriction and cell adhesion. Overall design: Zebrafish lateral line mRNA profiles of 36 hours wild type (WT) and NICD embryos were generated in triplicate, using HiSeq 2500 (Illumina).
Proliferation-independent regulation of organ size by Fgf/Notch signaling.
No sample metadata fields
View SamplesJQ1 is a small-molecule (BET family) bromodomain inhibitor that causes a contraceptive effect in mice by blocking spermatogenesis and reducing sperm motility.
Small-molecule inhibition of BRDT for male contraception.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sex, Specimen part
View SamplesPurpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sex, Specimen part
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