Presently, there is a deficiency of effective therapies designed to target clear cell renal cell carcinoma (ccRCC), with poor prognosis resulting in patients with advanced disease. Additionally, there is a lack of molecular factors which can be remedially targeted resulting in tumor specific inhibition, and therefore current therapeutic approaches often produce adverse side effects in patients. We identified that Stearoyl-CoA desaturase 1 (SCD1) was consistently overexpressed in patient ccRCC samples, and further investigation of SCD1 as a potential molecular target for ccRCC intervention utilizing a SCD1 inhibitor (A939572) resulted in tumor specific growth inhibition and induction of cell death. In order to understand the mechanism by which the SCD1 inhibitor mediated its anti-tumor effects, we performed gene array analysis and compared expression patterns between treated and untreated samples.
Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma.
Cell line, Treatment
View SamplesThe gene expression profile of blood drawn from healthy individuals was studied over a period of six months, at five time points. The gene expression profiles appeared to be constant over one month and to slightly vary over three months. A small proportion of genes were found to be differentially regulated according to gender. Differential gene regulation by age (in subjects 2555 years of age versus subjects > 55 years of age) was not observed.
A longitudinal study of gene expression in healthy individuals.
Sex, Age, Specimen part, Subject
View SamplesWe used microarrays to detail the global program of gene expression in cytokine stimulated effector CD8 T cells.
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Specimen part
View SamplesA better understanding of molecular changes during oral tumorigenesis may help defining new personalized prevention strategies. In order to test this hypothesis, we analyzed whole-genome expression changes in a murine model of oral carcinogenesis, induced by an oral carcinogen (4-NQO)
The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.
Sex, Specimen part
View SamplesWe investigated the route of neurotrophic cue delivery to the nerves
Loss of p53 drives neuron reprogramming in head and neck cancer.
Specimen part
View SamplesIn the urinary tract, smooth muscle (SM) is present in the renal pelvis, the ureter, the bladder and the urethra and plays a crucial role in the functional and structural integrity of these organs. In Tshz3 mutant ureters the myogenic program is not activated in the proximal region due to the absence of expression of myocardin (Myocd), a key regulator of SM differentiation. We set out to characterize TSHZ3-dependent mechanisms that participate to the process of ureteric smooth muscle cells (SMC) differentiation.
The tiptop/teashirt genes regulate cell differentiation and renal physiology in Drosophila.
Specimen part
View SamplesEBF1 is essential for B cell specification and commitment. To explore the dynamics of EBF1 initiated B cell programming, we performed EBF1 ChIP-seq, ATAC-seq, bisulfite-seq, RNA-seq and several histone ChIP-seq analyses at different stages of the transition from Ebf1-/- pre-pro-B to pro-B triggered by EBF1 restoration. We also performed Pax5 ChIP-seq in Ebf1-/- pre-pro-B cell and EBF1-restored pro-B cell to study the pioneering function of EBF1 that allows other transcription factors to access certain chromatin sites. Overall design: Time series RNA-Seq analysis during the differentiation from Ebf1-deficient pre-pro-B cell to EBF1-restored pro-B cell.
Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming.
Subject
View SamplesEed (embryonic ectoderm development) is a core component of the Polycomb Repressive Complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27). Trimethylated H3K27 (H3K27me3) can act as a signal for PRC1 recruitment in the process of gene silencing and chromatin condensation. Previous studies with Eed KO ESCs revealed a failure to down-regulate a limited list of pluripotency factors in differentiating ESCs. Our aim was to analyze the consequences of Eed KO for ESC differentiation. To this end we first analyzed ESC differentiation in the absence of Eed and employed in silico data to assess pluripotency gene expression and H3K27me3 patterns. We linked these data to expression analyses of wildtype and Eed KO ESCs. We observed that in wildtype ESCs a subset of pluripotency genes including Oct4, Nanog, Sox2 and Oct4 target genes progressively gain H3K27me3 during differentiation. These genes remain expressed in differentiating Eed KO ESCs. This suggests that the deregulation of a limited set of pluripotency factors impedes ESC differentiation. Global analyses of H3K27me3 and Oct4 ChIP-seq data indicate that in ESCs the binding of Oct4 to promoter regions is not a general predictor for PRC2-mediated silencing during differentiation. However, motif analyses suggest a binding of Oct4 together with Sox2 and Nanog at promoters of genes that are PRC2-dependently silenced during differentiation. In summary, our data further characterize Eed function in ESCs by showing that Eed/PRC2 is essential for the onset of ESC differentiation.
Polycomb protein EED is required for silencing of pluripotency genes upon ESC differentiation.
Specimen part, Cell line
View SamplesWe determined genome-wide nucleosome occupancy in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell type and protein specific binding preferences of transcription factors to sites with either low (e.g. Myc, Klf4, Zfx) or high (e.g. Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome depleted regions around transcription start and termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to their CpG-content or histone methylation marks. Throughout the genome nucleosome occupancy was dependent on the presence of certain histone methylation or acetylation modifications. In addition, the average nucleosome-repeat length increased during differentiation by 5-7 base pairs, with local variations for specific genomic regions. Our results reveal regulatory mechanisms of cell differentiation acting through nucleosome repositioning. Overall design: The Total RNA from ESCs, NPCs and MEFs was extracted by guanidinisothiocyanat/phenol extraction with the Trifast kit (Peqlab). Total RNA preparations were treated with DNase I, phenol/chloroform extracted and precipitated before further processing. RNAs were depleted of 5S, 5.8S, 18S and 28S rRNAs using the Human/Mouse/Rat Ribo-Zero rRNA Removal Kit (Epicentre) according to the manufacturer’s protocol. After rRNA depletion, RNAs were fragmented with a kit from Ambion. Libraries for Solexa sequencing were generated according to the standard Illumina protocol that comprised first strand cDNA synthesis, second strand cDNA synthesis, end repair, addition of a single A base, and adapter ligation. Sequencing was performed on the Illumina GAIIx (replicate 1) and Illumina HiSeq 2000 (replicate 2) platforms at the sequencing core facilities of the BioQuant in Heidelberg, Germany. RNA reads were aligned with TopHat. Further expression analysis was with the Genomatix software suite (Genomatix, Munich, Germany) and the Eldorado gene annotation. For each transcript a normalized expression value was calculated from the read distribution that accounts for the length differences using the program DEseq for the analysis of differential expression.
Genome-wide nucleosome positioning during embryonic stem cell development.
Specimen part, Cell line, Subject
View SamplesRNA expression in WT and jhd2? cells in various nutritional sources Overall design: Strand-specific total RNA was sequenced (Illumina stranded TruSeq, with dUTP second strand-incorporation) from wildtype and mutants cells, in biological replicates, normalized by RNA spike-in controls
Mitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation.
Cell line, Subject
View Samples