Mutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis.
Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo.
Specimen part, Treatment
View SamplesEstablishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that indomethacin and nimesulide influence expression of some genes among which are those coding for enzymes required for synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of indomethacin and nimesulide at the molecular level in terms of modulation of gene expression by these substances.
Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways.
Cell line
View SamplesVentricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. Overall design: Dll4 and Notch1 conditional KOs using Nfact1 and/or Tie2 driven Cre expression: RNA was isolated from pooled whole hearts of 8 (Nfact1) or 9 (Tie2) E9.5 embryos per replicate. Dll4flox;Nfatc1-Cre and WT siblings (4 KO and 4 WT replicates), Notch1flox;Nfatc1-Cre and WT siblings (3 KO and 2 WT replicates), Dll4flox;Tie2-Cre and WT siblings (3 KO and 3 WT replicates). Jag1, Jag2 and Jag1Jag2 conditional KOs using cTnT driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. Jag1flox;cTnT-Cre and WT siblings (3 KO and 3 WT replicates), Jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). Jag1flox;jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). MFng Gain Of Function using Tie2 driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. MFng;Tie2-Cre and WT siblings (4 GOF and 4 WT replicates). For Dll4, Noth1 and Jag1 KOs, libraries were prepared using the standard Illumina TrueSeq RNASeq library preparation kit and sequenced in a GAIIx Illumina sequencer using a 75bp single end elongation protocol. For Jag2 and Jag1Jag2 KOs and MFng GOF libraries were prepared prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced in a HiSeq2500 Illumina sequencer using a 61bp single end elongation protocol
Sequential Notch activation regulates ventricular chamber development.
No sample metadata fields
View SamplesTo identify genes that are regulated from the lncRNA ANRIL (EXON 13), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.
Disease
View SamplesTo identify genes that are regulated from the lncRNA ANRIL (EXON19), we designed inducible short hairpin RNA constructs and stable integrated them into HEK cells
Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1.
Disease
View SamplesAging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that de-repression of the nuclear receptors PPARa, PPAR?, and LXRa in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and for novel candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix factor Foxa2 and nuclear receptor co-repressor Hdac3 exhibit reciprocal binding pattern at PPARa targets contributing to gene expression changes that lead to steatosis in aged liver. Overall design: Genome-wide expression profiles (RNA-Seq) from young (3 months) and old (21 months) mouse livers
Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver.
No sample metadata fields
View SamplesUrothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer.
Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer.
Sex
View SamplesMembers of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared to other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We measured gene expression (Human Gene 1.0 ST Array, Affymetrix) in two series of experiments involving cells that were either susceptible or not susceptible to RV-C infection. In one experimental series, susceptible cells included whole sinus mucosal tissue specimens (n = 5), epithelial cell suspension from sinus tissue, and nasal epithelium obtained via brushing, while non-susceptible cells included monolayers of primary undifferentiated epithelial cells and transformed cell lines (n = 5). In a second experimental series, we compared three pairs of undifferentiated and fully differentiated (ALI) sinus epithelial cell cultures. We identified a total of 12 genes upregulated in RV-C susceptible cells (represented by 14 probe sets) encoding proteins localized to plasma membrane, and/or with predicted or functionally demonstrated receptor activity, including members of the Human MHC class II, stomatin, guanine nucleotide-binding, type I cytokine and atypical chemokine receptor and cadherin protein families.
Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.
Specimen part, Cell line, Subject
View Samplesaffy_xoo_rice - affy_xoo_rice - The Bacterial Leaf Blight disease of rice is due to Xanthomonas oryzae pv. oryzae. As for many pathogenic bacteria, it relies on a type 3 secretion system that is devoted to the injection of type 3 effectors into the eukaryotic host cell. These proteins are meant to suppress host basal defense responses and/or mimic some host regulatory function promoting bacterial survey in the plant. We are interested in the functional analysis of a subgroup of Xoo T3Es, that are specialized in host cell transcriptome remodelling. These effectors, therefore called TAL for Transcription Activator-Like proteins (also named AvrBs3/PthA-like), are often key virulence factors essential to Xoo pathogenicity such as the effector protein Talc of african Xoo strain BAI3. Our goal is to understand its function during disease development, by identifying rice host genes that are being directly up- or down-regulated by Talc. To that end, we aim at performing Affymetrix transcriptomic analysis, comparing leaf samples of a susceptible rice line inoculated with Xoo to leaves challenged with a Talc-deficient mutant and water-treated leaves. Highly induced genes are likely to be Talc primary targets and therefore potentially good susceptibility gene candidates.-The goal of the experiment is to identify the rice genes up- or down-regulated by the type III effector Talc from Xoo African strain BAI3, upon the inoculation of susceptible rice leaves 24 hours post-infection. To that end, the experimental design includes the inoculation of Nipponbare rice leaves with the virulent Xoo strain BAI3, that will be compared to Nipponbare rice leaves inoculated with a talc K.O. mutant strain and water.
Colonization of rice leaf blades by an African strain of Xanthomonas oryzae pv. oryzae depends on a new TAL effector that induces the rice nodulin-3 Os11N3 gene.
Specimen part
View SamplesThe host immune response against an infection requires the coordinated action of many diverse cell subsets that dynamically adapt to the pathogen threat. Here we combined WGCNA and DCQ to analyse time-resolved mouse splenic transcriptomes in acute and chronic LCMV infections. This approach allowed to better characterize the dynamic cell events occurring in complex tissues such as the induction of the adaptive T cell response which requires the coordination of monocytes/macrophages and CD8+ T cells. Overall design: mRNA profiles of CD8 T cells and macrophages (in duplicate days 0 and 7 post-infection) from C57BL/6 mice infected with 2x10E2 pfu of LCMV strain Docile, generated by deep sequencing.
Linking Cell Dynamics With Gene Coexpression Networks to Characterize Key Events in Chronic Virus Infections.
No sample metadata fields
View Samples