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SRP150331
Homo sapiens
12 Downloadable Samples
NextSeq 500
Description
Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties. Overall design: HeLa cells were cultured with DMEM plus 10% charcoal-stripped FBS. HeLa cells were treated in the presence of 100 nM triamcinolone acetonide (TA) for 4 hours. Cells were then collected for RNA-seq.
Publication Title
Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- NextSeq 500
Description
Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties. Overall design: Monocytes from healthy donors were cultured in the presence of 100 nM triamcinolone acetonide (TA), 100 nM Dexamethasone (Dex) or 100 nM Prednisolone (Pred) for 4 hours. Cells were then collected for RNA-seq.
Publication Title
Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
The mechanisms underlying enhancer activation and the extent to which enhancer-promoter rewiring contributes to spatiotemporal gene expression are not well understood. Using integrative and time resolved analyses we show that the extensive transcriptome and epigenome resetting during the conversion between 'serum-' and '2i'-states of mouse embryonic stem cells (ESCs) takes place with minimal enhancer-promoter rewiring that becomes more evident in primed-state pluripotency. Instead, differential gene expression is strongly linked to enhancer activation via H3K27ac. Conditional depletion of TFs and allele-specific enhancer analysis reveals an essential role for Esrrb in H3K27-acetylation and activation of 2i-specific enhancers. Restoration of a polymorphic ESRRB motif using CRISPR/Cas9 in a hybrid ESC-line, restores ESRRB binding and enhancer H3K27ac in an allele-specific manner but has no effect on chromatin interactions. Our study shows that enhancer activation in serum- and 2i-ESCs is largely driven by TF-binding and epigenetic marking in a hardwired network of chromatin interactions. Overall design: Time course analysis of mouse ESCs during transition between serum and 2i-cultured ESCs followed by integrative analysis of transcriptome by RNA-seq.
Publication Title
Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 80 Downloadable Samples
- Illumina HiSeq 2000
Description
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as LPS. We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time dependent manner. ChIP-seq, RNA-seq, WGBS and ATAC-seq data were generated. This analysis identified epigenetic programs in tolerance and trained macrophages, and the potential transcription factors involved. Overall design: Time-course in vitro culture of human monocytes. Two innate immune memory states can be induced in culture through an initial exposure of primary human monocytes to either LPS or BG for 24 hours, followed by removal of stimulus and differentiation to macrophages for an additional 5 days. Cells were collected at baseline (day 0), 1 hour, 4 hour, 24 hour and 6 days.
Publication Title
β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- IlluminaHiSeq2000
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Overall design: Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders.
Publication Title
Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Differential gene expression was analyzed for FACS sorted Math1::Cre; ROSA-tdTomato from hand dissected cochlear nuclei of wild type and Hoxa2/Hoxb2 mutant mice Overall design: In order to investigate the role of Hoxa2 and Hoxb2 transcription factors in a subset of cells of the cochlear nucleus, we generated double conditional knock-out by crossing the deleter line Math1::Cre crossed with Rosa tdTomato; Hoxa2fl/fl; Hoxb2fl/fl and Rosa tdTomato wild type background. FACS sorted cells from hand dissected cochlear nuclei were than processed and RNA-seq performed (see extract protocol and library construction protocol).
Publication Title
Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oxidative stress as a result of cigarette smoking is an important etiological factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. The activity of the transcriptional co-repressor Histone deacetylase-2 (HDAC2) is dramatically reduced in COPD and cells exposed to oxidative stress or cigarette smoke. Moreover, curcumin (diferuloylmethane), a dietary polyphenol, at concentrations upto 1uM specifically restores cigarette smoke extract (CSE)- or oxidative stress- impaired HDAC2 activity. The aim of this study was to therefore identify any links through those gene sets that are affected by oxidative stress and subsequent treatment with curcumin in order to determine whether or not this could explain the impact of curcumin on restoration of oxidant impaired HDAC2 transcriptional co-repressor activity.
Publication Title
Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 3000
Description
Keratinocytes isolated from one healthy donor were stimulated in triplicate for 24h with IL-36a, IL-36ß or IL-36? Overall design: Gene expression profile of IL-36 stimulated keratinocytes
Publication Title
An analysis of IL-36 signature genes and individuals with <i>IL1RL2</i> knockout mutations validates IL-36 as a psoriasis therapeutic target.
Sample Metadata Fields
Specimen part, Subject
View Samples