IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B or IL-36G. We identified some early IL-1B-specific responses (8 hours post-treatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 hours post-treatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 hours) followed by no response or repression (24 hours). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 + 24 hours). These involved up-regulation of ligands (IL1A, IL1B, IL36G) and activating proteases (CTSS), but also up-regulation of inhibitors such as IL1RN and IL36RN. Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, IBD, primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses. Overall design: Cultures were treated with truncated recombinant human IL-1B, IL-36A, IL-36B or IL-36G (10 ng/ml for IL-1B; 2000 ng/ml for IL-36 cytokines). Three cell lines were used (lines A, B and C) with samples processed in 4 batches. Samples within the same batch are comparable. Experiments were performed with 8 and 24 hours of cytokine treatment (n = 2-3 per time point).
RNA-Seq Analysis of IL-1B and IL-36 Responses in Epidermal Keratinocytes Identifies a Shared MyD88-Dependent Gene Signature.
Specimen part, Cell line, Treatment, Subject, Time
View SamplesTo evaluate the transcriptomes of lesional skin from different body parts of the same individual. Specifically, we conducted a transcriptomic study to investigate expression variability for diseased samples taken from different anatomic regions of same patient, and to compare the variability to between individuals variability. Overall design: 5 psoriasis patients, each with 4 psoriatic and 1 uninvolved skin biopsies. Totally 25 RNA-seq experiments conducted.
Transcriptional determinants of individualized inflammatory responses at anatomically separate sites.
Specimen part, Disease stage, Subject
View SamplesLow protein (LP) during gestation leads to low birth weight and poor fetal growth, with altered islet development and glucose intolerance in adulthood. Additionally, LP offspring fail to regenerate their -cells following depletion with streptozotocin (STZ), in contrast to control-fed offspring that are capable of -cell regeneration.
Cellular mechanisms underlying failed beta cell regeneration in offspring of protein-restricted pregnant mice.
Sex, Age, Specimen part, Treatment
View SamplesRNA was obtained from histologically normal bronchial epithelium of smokers during time of clinical bronchoscopy from relatively accessible airway tissue. Gene expression data from smokers with lung cancer was compared with samples from smokers without lung cancer. This allowed us to generate a diagnostic gene expression profile that could distinguish the two classes. This profile could provide additional clinical benefit in diagnosing cancer amongst smokers with suspect lung cancer.
Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer.
Sex, Age, Race
View SamplesThis study focused on transcription in the medial PFC (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized on tasks, attentional set shift and spatial memory, which depend on the mPFC and hippocampus, respectively. Differences in transcription associated with age and cognitive function were examined using RNA sequencing to construct transcriptomic profiles for the mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging associated with increased expression of immune and defense response genes and a decline in synaptic and neural activity genes. Importantly, we provide evidence for region specific transcription related to behavior. In particular, expression of transcriptional regulators and neural activity-related immediate-early genes (IEGs) are increased in the mPFC of aged animals that exhibit delayed set shift behavior; relative to age-matched animals that exhibit set shift behavior similar to younger animals. Overall design: The study contains 11 young and 20 aged rats for the mPFC and CA1 samples, which were used to investigate expression patterns associated with aging and behavior. White matter samples were used to investigate an age-related effect with 8 young and 9 aged rats.
Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex.
No sample metadata fields
View SamplesStaphylococcus aureus is a major human pathogen and resistant to numerous clinically used antibiotics. The first antibiotic developed for S. aureus infections was the nonribosomal petide secondary metabolite penicillin. We discovered cryptic nonribosomal peptide secondary metabolites, the aureusimines, made by S. aureus itself that are not antibiotics, but function as small molecule regulators of virulence factor expression. Using established rules and codes for nonribosomal peptide assembly we predicted these nonribosomal peptides, and used these predictions to identify them from S. aureus culture broths. Functional studies using global microarray and mouse bacteremia models established that the aureusimines control virulence factor expression and are necessary for productive infections. This is the first report of the aureusimines and has important implications for the treatment of drug resistant S. aureus. Targeting aureusimine synthesis may provide novel anti-infectives.
Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence.
No sample metadata fields
View SamplesAn evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with ADH-1 followed by melphalan in the setting of isolated limb infusion
Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma.
Disease, Disease stage, Treatment
View SamplesTranscriptional profiling after inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells
Transcriptional profiling in response to inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells.
Specimen part
View SamplesAt least six histone H1 variants exist in mammalian somatic cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be involved in the active regulation of gene expression. It is not well known whether the different variants have specific roles or regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. A different subset of genes is altered in each H1 knock-down.
Depletion of human histone H1 variants uncovers specific roles in gene expression and cell growth.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression.
Specimen part, Subject
View Samples