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 SamplesThe role of different proteins, Always Early (Aly), Spermatocyte Arrest (Sa), Ubi-p63E (Magn) on the gene expression in spermatocyte differentation was assessed by microarray
The polyubiquitin gene Ubi-p63E is essential for male meiotic cell cycle progression and germ cell differentiation in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
View SamplesThe effect of different loss of functions; kumgang (kmg or CG5204), dMi-2, and kmg and always early (aly) double on the gene expression in spermatocyte differentation was assessed by microarray.
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Specimen part
View SamplesThe only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication.
Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology.
Age
View SamplesTranscriptional silencing of terminal differentiation genes by the Polycomb group (PcG) machinery is emerging as a key feature of precursor cells in stem cell lineages. How, then, is this epigenetic silencing reversed for proper cellular differentiation? Here we investigate how the developmental program reverses local PcG action to allow expression of terminal differentiation genes in the Drosophila male germline stem cell lineage. We find that the silenced state, set up in precursor cells, is relieved through developmentally regulated sequential events at promoters once cells commit to spermatocyte differentiation. The programmed events include global down-regulation of PRC2, recruitment of hypophosphorylated RNA Polymerase II (Pol II) to promoters, as well as expression and action of cell-type specific homologs of subunits of TFIID (tTAFs). In addition, action of tMAC, a tissue specific version of the MIP/dREAM complex, is required both for recruitment of tTAFs to target differentiation genes and for proper cell-type specific localization of PRC1 components and tTAFs to the spermatocyte nucleolus. Together, action of the tMAC and tTAF cell-type specific chromatin and transcription machinery leads to loss of
Sequential changes at differentiation gene promoters as they become active in a stem cell lineage.
Time
View SamplesWe profiled the skeletal muscle transcriptome between wild type and aB-crystallin/HspB2 knock mice exposed to normal chow and high fat diets to examine the role of aB-crystallin/HspB2 in diet induced obesity. Combined with metabolic profiling of the mice, these data reveal that aB-crystallin/HspB2 is involved in the genesis of insulin resistance on a high fat diet, and we provide extensive RNA profiling to illuminate potential mechanistic insights into the muscle-specific role of aB-crystallin/HspB2. Overall design: Hind limb muscle mRNA profiles of wild type and aB-crystallin/HspB2 knock mice exposed to either normal chow or high fat diets using RNAseq analysis
αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.
No sample metadata fields
View SamplesShear stress is known to regulate endothelial cell orientation along the direction of flow. We asked wither cellular patterning along, in the absence of shear could have similar biological effects as shear.
Spatial patterning of endothelium modulates cell morphology, adhesiveness and transcriptional signature.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.
Specimen part
View SamplesWe used gene expression data from E-myc mouse lymphomas to test various genomic signatures and select lymphomas for further study
Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.
Specimen part
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