Amputation of heart tissue followed by regeneration of the heart. Samples were taken at 0 hpa (hours post-amputation), 6 hpa, 12 hpa, 24 hpa, 3 dpa and 5 dpa.
Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sex, Specimen part
View SamplesPurpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sex, Specimen part
View SamplesPurpose: The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due to immune defense activation, rarely occurs, we lack a biological rationale and predictive markers in selecting patients for immune therapy. Experimental Design: We performed unsupervised hierarchical clustering of global gene expression data from stage IV melanomas in 57 patients. For further characterization, we used immunohistochemistry of selected markers, genome-wide DNA copy number analysis, genetic and epigenetic analysis of the Q3 CDKN2A locus, and NRAS/BRAF mutation screening. Results: The analysis revealed four distinct subtypes with gene signatures characterized by expression of immune response, pigmentation differentiation, proliferation, or stromal composition genes. Although all subtypes harbored NRAS and BRAF mutations, there was a significant difference between subtypes (P < 0.01), with no BRAF/NRAS wild-type samples in the proliferative subtype. Additionally, the proliferative subtype was characterized by a high frequency of CDKN2A homozygous deletions (P < 0.01). We observed a different prognosis between the subtypes (P = 0.01), with a particularly poor survival for patients harboring tumors of the proliferative subtype compared with the others (P = 0.003). Importantly, the clinical relevance of the subtypes was validated in an independent cohort of 44 stage III and IV melanomas. Moreover, low expression of an a priori defined gene set associated with immune response signaling was significantly associated with poor outcome (P = 0.001). Conclusions: Our data reveal a biologically based taxonomy of malignant melanomas with prognostic effect and support an influence of the antitumoral immune response on outcome.
Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome.
Sex, Specimen part
View SamplesTo understand how an inhibition of the mitochondrial ATP synthase affects transcriptional programming and to identify potential candidates of the signaling machinery involved in ATP synthase deficiency responses, we used oligomycin on seedling liquid cultures. Seedlings were harvested at time points 0, 1 and 4 h after the start of oligomycin and control (EtOH) treatments. Already 1 h after addition of oligomycin a total of 102 genes were more than threefold up-regulated and 14 genes were repressed, with most of them showing persistent changes. After 4 h, 580 additional genes were more than threefold up-regulated, and 152 genes were repressed by oligomycin. Several genes for alternative NAD(P)H dehydrogenases and alternative oxidases (AOX1a, AOX1d and NDA1) were up-regulated early, and additional homologs (NDA2, NDB2, NDB4 and AOX1b) followed 4 h after the start of treatment. Several genes for subunits of complex I, complex IV and the ATP synthase were induced whereas hardly any genes encoding enzymes of glycolysis and the TCA cycle changed. Additionally, four of five hallmark genes for oxidative stress were increased by oligomycin. These genes are At2g21640 (UPOX), At1g19020, At1g05340 and At1g57630 and code for proteins of unknown function. Among oxidative stress proteins with known functions, several H2O2-responsive Glutathione-S-transferases and BCS1 (CYTOCHROME BC1 SYNTHESIS) were strongly up-regulated already after 1 h. BCS1 is induced by salicylic acid and independent of other reactive oxygen signaling (ROS) pathways, such as H2O2. The results indicate that several different ROS and defense signaling pathways were induced simultaneously by oligomycin. This is further corroborated by induction of several transcription factors of the WRKY and NAC families, which have been previously implicated in coordinating cellular defense signaling.
Downregulation of the δ-subunit reduces mitochondrial ATP synthase levels, alters respiration, and restricts growth and gametophyte development in Arabidopsis.
Specimen part, Treatment
View SamplesWe investigated the influence of SCFAs on human, monocyte derived DCs that represent a reliable in vitro model to study circulating DCs, one of the key regulators of our immune system. We studied the individual effect exerted by SCFA, the main metabolic end-products of fermentation by anaerobic bacteria in the gut, on the gene expression of immature and mature DC, exploring the potential of circulating bacterial metabolites to directly influence immune system cells. We found that SCFAs have little effect on the transcriptome of immature DC, whereas the transcriptome of mature DC was highly perturbed especially by butyrate and propionate. Our findings show an overall down-regulation of LPS-induced inflammatory responses and provide new insights into host-microbiome interactions.
The effect of short-chain fatty acids on human monocyte-derived dendritic cells.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesSimilar temporal expression kinetics of transcription factors in human and mouse osteoclast differentiation evaluated by microarray
Enhancer variants reveal a conserved transcription factor network governed by PU.1 during osteoclast differentiation.
Specimen part
View SamplesPurpose: The goal of the present study is to provide an independent assessment of the retinal transcriptome signatures of the C57BL/6J (B6) and DBA/2J (D2) mice and to enhance existing microarray datasets for accurately defining the allelic differences in the BXD recombinant inbred strains. Methods: Retinas from both B6 and D2 mice (3 of each) were used for the RNA-seq analysis. Transcriptome features were examined for both strains. Differentially expressed genes between the 2 strains were identified and bioinformatic analysis was performed to analyze the transcriptome differences between B6 and D2 strains, including Gene ontology (GO) analysis, Phenotype and Reactome enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The RNA-seq data were then directly compared with one of the microarray datasets (DoD Retina Normal Affy MoGene 2.0 ST RMA Gene Level Microarray Database) hosted on GeneNetwork (www.genenetwork.org). Results: RNA-seq provided an in-depth analysis of the transcriptome of the B6 and D2 retina with a total of more than 30,000,000 reads per sample. Over 70% of the reads were uniquely mapped, resulting in a total of 18,100 gene counts for all 6 samples. 1,665 genes were differentially expressed, with 858 of these more highly expressed in B6 and 807 more highly expressed in D2. Several molecular pathways were differentially active between the two strains, including the retinoic acid metabolic process, endoplasmic reticulum lumen, extracellular matrix organization, and PI3K-Akt signaling pathway. The most enriched KEGG pathways were the pentose and glucuronate interconversions pathway, the cytochrome P450 pathway, protein digestion and absorption pathway and the ECM-receptor interaction pathway. Each of these pathways had a more than 4-fold enrichment. The DoD normal retina microarray database provided expression profiling for 26,191 annotated transcripts for B6 mouse, D2 mouse and 53 BXD strains. A total of 13,793 genes in this microarray dataset were comparable to the RNA-seq dataset. For both B6 and D2, the RNA-seq data and microarray data were highly correlated with each other (Pearson's r = 0.780 for B6 and 0.784 for D2). Our results suggest that the microarray dataset can reliably detect differentially expressed genes between the B6 and D2 retinas, with a positive predictive value of 45.6%, and a negative predictive value of 93.6%. Examples of true positive and false positive genes are provided. Conclusions: Retinal transcriptome features of B6 and D2 mouse strains provide a useful reference for a better understanding of the mouse retina. Generally, the microarray database presented on GeneNetwork shows good agreement with the RNA-seq data, while we note that any allelic difference between B6 and D2 should be verified with the latter. Overall design: Retinal mRNA profiles of 2 strains of mice, C57BL/6J and DBA/2J, were generated by deep sequencing, in triplicate, using Illumina TruSeq Stranded Total RNA kit.
RNA sequencing profiling of the retina in C57BL/6J and DBA/2J mice: Enhancing the retinal microarray data sets from GeneNetwork.
Specimen part, Cell line, Subject
View SamplesWe assessed genome-wide expression of available pretreatment specimens from CLL patients enrolled in REACH, a study of fludarabine and cyclophosphamide FC or R-FC (addition of rituximab to FC) in relapsed CLL, to understand the disease heterogeneity and explore genes that may be prognostic or predictive of benefit from R-FC treatment. REACH (NCT00090051) was registered at www.clinicaltrials.gov.
PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.
Specimen part, Disease stage, Subject
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