To study the senescence gene signatures in the cells, which were genetic SMARCB1 depleted or treated with aurora kinase inhibitors or etoposide, we performed next generation RNA sequencing on these cell, and ''FRIDMAN_SENESCENCE_UP'' geneset was used to determine the enrichment of senescence-related genes. The RNA sequencing results include (1) A375 cells and SMARCB1 depleted counterparts. (2) A549 cells and aurora kinase inhibitor (Alisertib, barasertib or tozasertib) or etoposide treated counterparts. Overall design: RNA seq data of A375_gSMARCB1 + A549_etoposide, Aurora kinases inhibitors treated, to check senescence gene expression signature one replicate of A375 cells parental V.S SMARCB1 KO (by CRISPR) + duplicates of A549 parental V.S etoposide, or 3 indepdent aurora kinase inhibitors (MLN8237/Alisertib, VX680/Tozasertib, AZD1132/Barasertib)
High-Throughput Functional Genetic and Compound Screens Identify Targets for Senescence Induction in Cancer.
Disease, Disease stage, Cell line, Subject
View SamplesBRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance, which is frequently caused by reactivation of the Mitogen Activated Protein Kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor (HDACi) vorinostat represses SLC7A11 that leads to a lethal increase in the already elevated levels of ROS in drug-resistant cells, thereby causing selective apoptotic death of only the drug resistant tumor cells. Consistently, treatment of BRAF inhibitor-resistant melanoma with HDACi in mice results in a dramatic tumor regression. In a study in patients with advanced BRAF+MEK inhibitor resistant melanoma, we find that HDACi can selectively ablate drug-resistant tumor cells, providing clinical proof of concept for the novel therapy identified here. Overall design: one replicate of RNA Seq data A375, A375R, A375DR vorinostat treated and patient samples pre- post- vorinostat treatment
An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential.
Specimen part, Disease, Disease stage, Cell line, Treatment, Subject
View SamplesGroup living animals must be able to express different behavior profiles depending on their social status. This implies that the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. Here we show for the first time that what triggers the switch between status-specific neurogenomic states is not the objective structure of the social interaction but rather the subjects perception of its outcome. For this purpose we had male zebrafish fight either a real opponent or their own image on a mirror. Massive changes in the brain transcriptome were observed in real opponent fighters, which experience either a victory or a defeat. In contrast, mirror fighters, which had no information on fight outcome despite expressing aggressive behavior, failed to activate a neurogenomic response. These results indicate that, even in cognitively simple organisms such as zebrafish, neurogenomic responses underlying changes in social status rely on cognitive appraisal.
Assessment of fight outcome is needed to activate socially driven transcriptional changes in the zebrafish brain.
Specimen part
View SamplesE-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach.
Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein isoform that increases gastric cancer cell invasion and angiogenesis.
Specimen part, Cell line
View SamplesThere is an association between transcriptome and the exercise-related phenotype. Peripheral blood cells suffer alterations in the gene expression pattern in response to perturbations caused by exercise. The acute response to endurance activates stress and inflammation, as well as growth and tissue repair responses.
PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesIn order to characterize defense responses not only cytologically, but also on the transcript level, genome-wide sequencing of mRNA isolated from non-infected control leaves and from leaves inoculated either with the WT or with GLS1 overexpressing strains was performed, using Illumina Next Generation Sequencing Technology. In order to identify transcripts specifically induced in leaves infected by ß-1,3-glucan-exposing strains, transcript patterns of leaves inoculated with GLS1 overexpressing PtrpC:GLS1 strains were compared with those of the WT. In PtrpC:GLS1-inoculated leaves, a total of 2179 genes were more than 2.5-fold increased, with many genes known as genes typically up-regulated in PAMP-triggered defense responses. These genes include genes encoding PR proteins enzymes involved in cell wall re-inforcemen, and terpene synthases possibly involved in phytoalexin synthesis. Furthermore, increased transcript abundance of genes encoding serine-threonine receptor-like kinases calmodulin, as well as zinc-finger and WRKY transcription factors have been identified. Other up-regulated genes encode proteins involved in protein degradation, i.e. proteases, ubiquitin ligases, as well as enzymes involved in synthesis of auxin or cytokinin phytohormones. In comparison, 2164 genes were more than 2.5-fold down-regulated in maize leaves infected by PtrpC:GLS1 strains, as compared to WT-infected leaves. Several of the encoded proteins are known susceptibility factors. Forty-six down-regulated genes code for proteins containing iron or manganese, or are involved in uptake of these ions, suggesting major re-arrangement of the redox-status in maize leaves after ß-glucan perception. Overall design: Examination of plant defense responses in maize plants inoculated with 2 different Colletotrichum graminicola strains.
Infection structure-specific expression of β-1,3-glucan synthase is essential for pathogenicity of Colletotrichum graminicola and evasion of β-glucan-triggered immunity in maize.
Age, Subject, Time
View SamplesPublic information is widely available at low cost to animals living in social groups. For instance, bystanders may eavesdrop on signaling interactions between conspecifics and use it to adapt their subsequent behavior towards the observed individuals. This social eavesdropping ability is expected to require specialized mechanisms such as social attention, which selects social information available for learning. To begin exploring the genetic basis of social eavesdropping, we used a previously established attention paradigm in the lab to study the brain gene expression profile of male zebrafish in relation to the attention they have paid towards conspecifics involved or not involved in agonistic interactions. Microarray gene chips were used to characterize their brain transcriptomes based on differential expression of single genes and gene sets. These analyses were complemented by promoter region-based techniques. Using data from both approaches, we further drafted protein interaction networks. Our results suggest that attentiveness towards conspecifics, whether interacting or not, activates pathways linked to neuronal plasticity and memory formation. The network analyses suggested that fos and jun are key players on this response, and that npas4a, nr4a1 and egr4 may also play an important role.
Brain Transcriptomic Response to Social Eavesdropping in Zebrafish (Danio rerio).
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis.
Specimen part
View SamplesControversy regarding genetically modified (GM) plants and their potential impact on human health contrasts with the tacit acceptance
Microarray analyses reveal that plant mutagenesis may induce more transcriptomic changes than transgene insertion.
Specimen part
View SamplesThat commensal bacteria can influence intestinal inflammation has been observed using other models of chronic colitis. Loss of IL-10, a major immunosuppressive cytokine, induces spontaneous colitis in mice. The incidence of spontaneous polyp formation in IL-10-deficient mice was also completely eliminated in the absence of STING
STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis.
Specimen part
View Samples