Alzheimers disease (AD) is the most common neurodegenerative dementia. Around 10% of cases present an age of onset before 65 years-old, which in turn can be divided in monogenic or familial AD (FAD) and sporadic early-onset AD (EOAD). Mutations in PSEN1, PSEN2 and APP genes have been linked with FAD. The aim of our study was to describe the brain whole-genome RNA expression profile of the posterior cingulate area in EOAD and FAD caused by PSEN1 mutations (FAD-PSEN1). 14 patients (7 EOAD and 7 FAD-PSEN1) and 7 neurologically healthy controls were selected and samples were hybridized in a Human Gene 1.1 microarray from Affymetrix. When comparing controls with EOAD and controls with FAD-PSEN1, we found 3183 and 3351 differentially expressed genes (DEG) respectively (FDR corrected p<0.05). However, any DEG was found in the comparison of the two groups of patients. Microarrays were validated through quantitative-PCR of 17 DEG. In silico analysis of the DEG revealed an alteration in biological pathways related to calcium-signaling, axon guidance and long-term potentiation (LTP), among others, in both groups of patients. These pathways are mainly related with cell signalling cascades, synaptic plasticity and learning and memory processes. In conclusion, the altered biological final pathways in EOAD and FAD-PSEN1 are highly coincident. Also, the findings are in line with those previously reported for late-onset AD (LOAD, onset >65 years-old), which implies that the consequences of the disease at the molecular level are similar in the final stages of the disease.
A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer's disease.
Sex
View SamplesTumor cells utilize the so-called Warburg effect to allow for rapid proliferation with glucose as the main nutrient. We show here that, although PKCz is critical for that effect, its deficiency promotes the plasticity necessary for nutrient-stressed cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway, empowering them to survive and proliferate in the absence of glucose. We show that PKCz deficiency enhances glutamine utilization and expression of two key enzymes of the pathway, PGHDGH and PSAT1, in cells cultured in the absence of glucose. The loss of PKCz in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, while patients with low levels of PKCz have a poor prognosis. Taken together, this suggests that PKCz is a critical metabolic tumor suppressor.
Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis.
Cell line, Treatment
View SamplesWe have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (abbreviated as B) was substituted for that of A/J mice (ChrY<A>), cardiomyocytes from the resulting 'chromosome substitution' C57BL/6J-chrY<A> strain (abbreviated as B.Y) were smaller than that of their C57BL/6J counterparts. In reverse, when chrY<A> from A/J mice was substituted for that of chrY<B>, cardiomyocytes from the resulting A/J-chrY<C57> strain were larger than in their A/J counterparts. We further used these strains (B and the consomic B.Y) to test whether the origin of chrY could also be linked to differences in the profile of gene expression in their cardiac left ventricles in adult mice where either sham surgery (intact animals) or castration has been performed at 3-4 weeks of age..
Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone.
Sex
View SamplesMutants in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. This data shows the changes in gene expression profile associated to mutations in l(3)mbt, both in situ in third instar larval brains and in tumors cultured for 1 5 and 10 (T1, T5, T10) rounds of allograft culture
Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila.
No sample metadata fields
View SamplesAcute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. In order to elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness in AQM, gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.
Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model.
Sex, Specimen part, Disease, Disease stage
View SamplesDiamond-Blackfan anemia (DBA) is characterized by anemia and cancer susceptibility, and is caused by mutations in ribosomal genes, including Rpl11. Here, we report that Rpl11-heterozygous embryos are not viable, and homozygous deletion of Rpl11 in adult mice results in death within a few weeks, accompanied by bone marrow aplasia and intestinal atrophy. Importantly, deletion of a single Rpl11 allele in adult mice results in anemia associated to decreased erythroid progenitors and defective erythroid maturation. These phenotypes are also present in mice transplanted with inducible heterozygous Rpl11 bone marrow, indicating a cell-autonomous role of RPL11 in erythropoiesis. Additionally, fibroblasts lacking one or both Rpl11 alleles show defective p53 activation upon ribosomal stress or DNA damage. Furthermore, fibroblasts and hematopoietic tissues from heterozygous Rpl11 mice present higher basal cMYC levels. Accordingly, heterozygous Rpl11 mice are highly susceptible to radiation-induced lymphomagenesis. We conclude that Rpl11-deficient mice recapitulate DBA disorder, including cancer predisposition. Overall design: RNAseq profiles of bone marrow hematopoietic progenitors cells from WT (Rpl11+/+:: Tg.UbC-CreERT2) and LOX (Rpl11+/lox::Tb.Ub-CreERT2) mice, n=4 independent animals per genotype
Partial Loss of Rpl11 in Adult Mice Recapitulates Diamond-Blackfan Anemia and Promotes Lymphomagenesis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesPurpose: The goal of this study is to compare the transcriptome profilling (RNA-seq) of inflorescences infected with tobacco ratle virus (TRV) to mock inoculated inflorescences (negative controls), in Arabidopsis plants Methods: Inflorescences of systemically TRV infected or mock-inoculated plants were collected from more than 40 independent Arabidopsis plants, at 14 days post-inoculation (dpi). TRV and mock mRNA profiles were generated by deep sequencing by Illumina HiSeq 2000. The sequence reads that passed quality filters (SOAPnuke) were analysed by Burrows-Wheeler (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. Genes and isoforms were quantified by RSEM sofware package. qRT-PCR validation was performed using TaqMan and SYBR Green assays. Results: Here we report a significant repression of DNA methylation genes in inflorescences of Arabidopsis plants infected with Tobacco rattle virus (TRV) that coincides with dynamic changes in methylation at the whole genome level. Arabidopsis mutants deficient in DNA methylation were more resistant to this virus in early colonized tissues but more susceptible at later time points of infection, indicating that DNA methylation was critical to control both proliferation and antiviral defense. We found that TRV interference with DNA methylation leads to changes in the methylation and trancriptional status of transposable elements (TEs), including TEs located in the promoter of disease resistance genes that were significantly repressed in plants exposed to TRV. Activation of both TEs and their nearby disease resistance genes was altered in a range of hypo- and hyper-methylated Arabidopsis mutants, indicating that perturbations in DNA methylation contributes to modulate their expression in infected plants. Conclussion: Our study showed that TRV interferes with DNA methylation to alter the transcriptional silencing of TEs, which in turn compromises the expression of neighboring disease resistance genes. Overall design: TRV and mock mRNA profiles were generated from Arabidopsis inflorescences by deep sequencing with Illumina HiSeq 2000.
Crosstalk between epigenetic silencing and infection by tobacco rattle virus in Arabidopsis.
Specimen part, Subject
View SamplesIn mammals, resident dermal macrophages (Ms) are subverted by Leishmania (L.) amazonensis amastigotes as host cells permissive for parasite multiplication. These Leishmania are living within a communal parasitophorous vacuole (PV) and are expected to trigger unique M transcriptional signatures. We performed a transcription profiling of mouse Ms harboring amastigotes to get insights into their reprogramming as host cells for parasite multiplication. BALB/c mouse bone marrow-derived Ms were either loaded or not with four amastigotes on average. Twenty four hours later, when amastigotes multiply, total RNA from M cultures was prepared, amplified and hybridized onto Affymetrix Mouse430_2 GeneChips. The outcome recorded a total of 1,248 probe-sets showing significant differential expression. Comparable fold-change values for a handful of genes were obtained between Affymetrix technology and the more sensitive RTqPCR method. Ingenuity Pathway Analysis software pinpointed the up-regulation of the sterol biosynthesis pathway (P-value = 1.31e-02) involving several genes (1.95 to 4.30 fold-change values), and the modulation of various genes involved in polyamine synthesis and in pro/counter-inflammatory signaling. Our findings suggest that amastigotes exploit the M lipid and polyamine pathways to multiply efficiently, and induce a counter-inflammatory environment to expand their dermis niche.
Transcriptional signatures of BALB/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.
No sample metadata fields
View SamplesNext to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS senses signals from outside the cell and transmits them into the cytoplasm. It consists of a TonB-dependent outer membrane receptor, a cytoplasmic membrane-localized sigma factor regulator (or anti-sigma factor), and an extracytoplasmic function (ECF) sigma factor. Upon perception of the extracellular signal by the receptor the ECF sigma factor is activated and promotes the transcription of a specific set of gene(s). Although most P. aeruginosa ECF sigma factors are involved in the regulation of iron uptake, we have identified a novel ECF sigma factor (PA0675) involved in the regulation of virulence. By microarray analysis of cells overexpressing PA0675 from the pMUM3 plasmid we have identified the genes regulated by this sigma factor.
A Novel extracytoplasmic function (ECF) sigma factor regulates virulence in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesWOX5 maintains columella stem cells in the Arabidopsis root and prevents their differentiation. In order to understand the molecular mode of WOX5 action the genes differentially expressed by WOX5 inducible over-expression were determined by analysis of microarray hybridizations. Seedlings transformed with a dexamethasone inducible WOX5 construct were induced for one or four hours with dexamethasone or a mock solution. Other seedlings were treated one hour with cycloheximide ( a protein synthesis inhibitor to reduce secondary transcriptional effects after WOX5 activation) and either dexamethasone or a mock solution. Root tips were harvested, RNA extracted, and the RNA samples prepared for hybridization to Affymetrix microarrays. Potential target genes of WOX5 were further analyzed by transcriptional markers, qPCR and EMSA (electrophoretic mobility shift assay).
Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression.
Specimen part, Compound, Time
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