Genetically engineered mouse models of cancer represent valuable biological tools that can be used to filter genome-wide expression datasets generated from human prostate tumours, and identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNASeq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. In order to identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we identified the serine/threonine kinase MELK as a potential therapeutic target in prostate cancer. MELK was overexpressed in both human and murine prostate cancers, and high expression of MELK was associated with biochemical recurrence in prostate cancer patients. Overall design: 92 Samples
Identification of potential therapeutic targets in prostate cancer through a cross-species approach.
Cell line, Subject
View SamplesTranscription is a major contributor to genome instability. A main cause of transcription-associated instability relies on the capacity of transcription to stall replication. Such genome instability is increased in RNAPII mutants.
RNA polymerase II contributes to preventing transcription-mediated replication fork stalls.
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View SamplesImmunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know very little about the genetic influences on this phenomenon.
Age-specific variation in immune response in Drosophila melanogaster has a genetic basis.
Sex, Age, Specimen part
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Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sex, Age, Specimen part
View SamplesAnalysis of gender differential gene expression levels in mouse liver.
Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRα) determines male-female differences in the expression of hepatic lipid processing genes in mice.
Sex, Age, Specimen part
View SamplesVascular hypoperfusion is a pathological phenomenon in the glaucomatous optic nerve head. We report transcriptional responses in GFAP-negative LC cells exposed to in-vitro hypoxic stress (1%O2).
Hypoxia regulated gene transcription in human optic nerve lamina cribrosa cells in culture.
Specimen part
View SamplesTranscriptional changes upon elicitor treatment over time (0, 30, 60 min) have been analysed with the A.thaliana Landsberg (wt) and fls2-17 (flagellin receptor mutant).
Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation.
Age, Compound, Time
View SamplesIn the present study, we have investigated the effect of CpG Oligodeoxynucleotides (CpG-ODN) on the outcome of Plasmodium infection of the mosquito vectors Anopheles stephensi and Anopheles gambiae and on the modulation of mosquito immunity to Plasmodium. Anopheles mosquitoes inoculated with CpG-ODN showed significant reduction of Plasmodium infection rate and intensity. Microarrays were used to profile transcription of fat-body from CpG-ODN-treated mosquitoes. Mosquitoes were dissected 18h after ODN inoculation (immediately before feeding). Batches of 20 to 30 fat bodies (abdomen without midgut, ovaries and malpighian tubule]) were dissected in cold DEPC-treated phosphate-buffered saline (PBS) and processed for RNA preparation. Mosquitoes treated with CpG-ODNs are less susceptible to Plasmodium infection. Transcription profile of fat body indicates that protection was associated with coagulation/wound healing, while melanization appears to be depressed.
CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.
Sex, Specimen part, Treatment
View SamplesRett syndrome (RTT) is a severe neurodevelopmental disorder that is caused by mutations in the gene methyl-CpG-binding-protein-2 (MECP2). However, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. In this study, we stimulated MeCP2-null cortical neurons (in vitro) and brains (in vivo) of a RTT mouse model to explore the effect of the loss of MeCP2 function on the activity-dependent transcriptomes of the cortex and hippocampus, respectively, using RNA-seq. These analyses revealed that the loss of MeCP2 results in aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity. Overall design: For in vitro experiments, RNA-seq was performed on MeCP2-null (MT) and wild-type (WT) neuron-enriched cortical cultures that were either treated (T) with KCl for 3hr or not treated (N), after 10 days in culture. For in vivo experiments, RNA-seq was performed on hippocampi of MeCP2-null (MT) and wild-type (WT) mice that were either treated with kainic acid for 40 or 68 minutes, or not treated.
Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome.
Specimen part, Treatment, Subject, Time
View SamplesOur analysis indicates that at least 37% of the transcriptome mobilized by KNAT1 is potentially dependent on this interaction, and includes genes involved in secondary cell wall modifications and phenylpropanoid biosynthesis. Overall design: Seven-day-old Arabidopsis wild-type (No-0) and 35S::KNAT1 seedlings growing in MS plates under continuous light were transferred to a liquid growing medium supplemented with 10 µM paclobutrazol (PAC) for 18 h. Seedlings were then incubated with 10 µM PAC+100 µM GA3 or maintained in 10 µM PAC for 5 h.
Regulation of xylem fiber differentiation by gibberellins through DELLA-KNAT1 interaction.
Specimen part, Treatment, Subject
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