Melanomas are often infiltrated by activated inflammatory cells. Thus, melanoma cells are very likely stimulated by inflammatory cytokines.
Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.
Cell line
View SamplesThe aim of this work was to identify functional features that are specific of human Treg cells, through the identification of genes that are differentially expressed: 1/ in activated Treg clones versus activated Thelper clones; 2/ in Th clones activated in the presence versus the absence of TGFb; 3/ in suppressed Th clones, i.e. Th clones activated in the presence of Treg clones, versus controls.
Comparison of stable human Treg and Th clones by transcriptional profiling.
No sample metadata fields
View SamplesArp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt and ARPC4 ko epidermis
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Specimen part, Cell line, Subject
View SamplesArp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt, ARPC4 ko and EGFP-Nrf2 expressing keratinocytes.
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Specimen part, Cell line, Subject
View SamplesProbiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications.
Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways.
Specimen part
View SamplesSome commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-B-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli.
Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.
No sample metadata fields
View SamplesWe used genome-wide expression analyses to study the response of Saccharomyces cerevisiae to stress throughout a 15-day wine fermentation. Forty percent of the yeast genome significantly changed expression levels to mediate long-term adaptation to an environment in which ethanol is both a stressor and a carbon source. Within this set, we identify a group of 223 genes, designated as the Fermentation Stress Response (FSR), that are dramatically and permanently induced; FSR genes exhibited changes ranging from four-to eighty-fold. The FSR is novel; 62% of the genes involved have not been implicated in global stress responses and 28% of the genes have no functional annotation. Genes involved in respiratory metabolism and gluconeogenesis were expressed during fermentation despite the presence of high concentrations of glucose. Ethanol, rather than nutrient depletion, was responsible for entry of yeast cells into stationary phase. Ethanol seems to regulate yeast metabolism through hitherto undiscovered regulatory networks during wine fermentation.
Dynamics of the yeast transcriptome during wine fermentation reveals a novel fermentation stress response.
No sample metadata fields
View SamplesCytotoxic T cells confer a prognostic benefit in many tumors, including ovarian cancer. We and others have previously identified a subset of CD8+ T cells, namely CD103+CD8+ T cells, that seems to have a better prognostic effect. The aim of this study is to identify how these CD103+ T cells differ from CD103-CD8+ T cells on mRNA level in human samples of ovarian cancer. Overall design: mRNA profiles of 10 pools of 20 cells CD103+CD8+, 10 pools of 20 cells CD103-CD8+, 20 single-cells CD103+CD8+, 20 single-cells CD103-CD8+ were generated from TILs of 3 ovarian cancers (high-grade serous ovarian cancer) by SMARTseq2
A Transcriptionally Distinct CXCL13<sup>+</sup>CD103<sup>+</sup>CD8<sup>+</sup> T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.
Subject
View SamplesMice of indicated ages and genotypes were perfused and their brains dissected and dissociated. Cells were fixed, immunolabeled and FACS sorted. RNA was extracted from neuron, astrocyte, and microglial cell populations. Typical RIN=4-5 for neurons, 6-8 for astrocytes, and 5-7 for microglia. Typical RNA yields ~100ng for neurons, ~20ng for microglia, and ~10ng for astrocytes. cDNA was generated from up to 25 ng of total RNA using Nugen’s RNA-Seq method for low-input RNA samples, Ovation RNA-Seq System V2 (NuGEN). (Per manufacturers instructions, total RNA was neither depleted of rRNA nor polyA-selected.) 1 µg of sheared cDNA was taken into further processing, starting at end repair step, using Illumina’s TruSeq RNA Sample Preparation Kit v2 (Illumina). The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0006149 Overall design: Astrocytes, microglia and neurons were sorted from 7- or 13-month old PS2APP or non-transgenic mice, 4 = n = 7 per group.
Untangling the brain's neuroinflammatory and neurodegenerative transcriptional responses.
Age, Specimen part, Subject
View SamplesNormal mice were injected i.p. with LPS or saline. 24h later, perfused brains were dissociated. Cells were fixed, immunolabeled and FACS sorted. RNA was extracted from neuron, astrocyte, and microglial cell populations. Typical RIN=4-5 for neurons, 6-8 for astrocytes, and 5-7 for microglia. Typical RNA yields ~100ng for neurons, ~20ng for microglia, and ~10ng for astrocytes. cDNA was generated from up to 25 ng of total RNA using Nugen''s RNA-Seq method for low-input RNA samples, Ovation RNA-Seq System V2 (NuGEN). (Per manufacturers instructions, total RNA was neither depleted of rRNA nor polyA-selected.) 1 µg of sheared cDNA was taken into further processing, starting at end repair step, using Illumina''s TruSeq RNA Sample Preparation Kit v2 (Illumina). The "SAMID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0005404 Overall design: Astrocytes, microglia and neurons were sorted from LPS or saline treated mice. n=4 or 5 per group.
Untangling the brain's neuroinflammatory and neurodegenerative transcriptional responses.
Specimen part, Treatment, Subject
View Samples