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SRP174051
Mus musculus
12 Downloadable Samples
Illumina Genome Analyzer
Description
Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the anti-inflammatory properties of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a serious problem in the management of inflammatory diseases and occurs frequently. The strong pro-inflammatory cytokine TNF induces an acute form of GCR, not only in mice, but also in several cell lines, e.g. in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-induced GR-dependent gene expression. We report that TNF has a significant and broad impact on the transcriptional performance of GR, but no impact on nuclear translocation, dimerization or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome is strongly modulated by TNF. One GR cofactor that interacts significantly less with the receptor under GCR conditions is p300. NF?B activation and p300 knockdown both reduce transcriptional output of GR, whereas p300 overexpression and NF?B inhibition revert TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis is supported by FRET studies. This mechanism of GCR opens new avenues for therapeutic interventions in GCR diseases Overall design: Examination of GR induced gene expression in 4 conditions (1 control: NI and 3 treated: DEX, TNF, TNFDEX) starting from 3 biological replicates
Publication Title
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Illumina HiSeq 2500
Description
We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions. Overall design: RNA-seq on 11 samples with 2-3 replicates per exposure/stimulation group (each replicate contains 3 pooled samples)
Publication Title
Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
This study describes the transcriptome profiling of: 1) MM-401, a MLL1 specific inhibitor in MAF9 cells; 2) Comparation of the transcriptone profilings of MM-401,EPZ-5676 (Dot1L inhibitor), MI-2(Menin inhibitor) and iBET(Brd4 inhibitor) in MAF9 leukemia cells. Overall design: RNA-Seq profiling on mouse MAF9 leukemia cells. Biological duplicates of each sample are labled as rep1/2.
Publication Title
MLL1 and MLL1 fusion proteins have distinct functions in regulating leukemic transcription program.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Identifying target genes of the two human chromatin remodeling enzymes CHD3 and CHD4 Methods: see below in protocols Results: Libraries were sequenced on Illumina HiSeq2000 platform resulting in 37-71 Mio 50 bp paired-end reads per sample. We identified 16 (i) and 115 (ii) distinctly regulated genes when CHD3-GFP (i) or CHD4-GFP (ii) were overexpressed. Nine genes seem to be commonly regulated by CHD3 and CHD4. We successfully validated four genes from our RNA-seq via qPCR with two new (independent from those, used for RNA-seq) biological replicates. Conclusion: CHD3 and CHD4 regulate distinct genes. Overall design: Total RNA was prepared from 24 hours induced (1 ng/µl Dox) and non-induced Flp-In™ T-REx™ 293 cells, expressing GFP, hCHD3-GFP (UniProt: Q12873) or hCHD4-GFP(UniProt Q14839). Library preparation and Illumina Sequencing was perfprmed by EMBL GeneCore facility in Heidelberg (Germany: Dr. Vladimir Benes)
Publication Title
CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The intestinal immune system must elicit robust immunity against harmful pathogens but restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c macrophages in the lamina propria (LP) that express several anti-inflammatory molecules including interleukin 10 (IL-10), but little or no pro-inflammatory cytokines, even upon stimulation with Toll-like receptor (TLR) ligands. These macrophages induced, in a manner dependent on IL-10, retinoic acid and exogenous transforming growth factor-, differentiation of FoxP3+ regulatory T cells. In contrast, LP CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by LP macrophages, indicating that a dynamic interplay between these subsets may influence the balance between immune activation and tolerance.
Publication Title
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of inflammatory pathways in human IBD
Publication Title
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Pathological bone changes differ considerably between inflammatory arthritic diseases, and most studies have focused on bone erosion. Collagen Induced Arthritis (CIA) is a model for Rheumatoid Arthritis, which, in addition to bone erosion, demonstrates bone formation at the time for clinical manifestations. The objective of this study was to use the CIA model to study bone remodelling by performing a gene expression profiling time-course study on the CIA model.
Publication Title
Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Etiolated Arabidopsis seedlings open their cotyledons and halt rapid elongation of hypocotyl when exposed to light (de-etiolation). Major light responsive components in this process have been identified and signaling pathways revealed, yet how the organ-specific light responses are achieved remains unknown. Here we report that a developmental regulator TCP4 (TEOSINTE BRANCHED1, CYCLOIDEA, and PCF) participates in photomorphogenesis and facilitates light-induced cotyledon-opening. We demonstrate that TCP4-like transcriptional factors, which predominantly express in cotyledons of both light and dark seedlings, activate SAUR16 and SAUR50 in response to light. Light repressor PIF3 (or PIFs, phytochrome-interacting factors), which accumulates in etiolated seedlings and rapidly declines upon light exposure, inhibits TCP4 promoter-binding and prevents activation of SAUR16/50 in darkness. Our study reveals how an interplay between light responsive factors and developmental regulators leads to signal-dependent and tissue-specific regulation of gene expressions, which ultimately resulted in organ-specific light responses during de-etiolation. Overall design: Cotyledon mRNA profiles of 4-day-old dark grown Col, mTCP4#4 and mTCP4#10 seedlings were generated by deep sequencing.
Publication Title
The Transcription Factors TCP4 and PIF3 Antagonistically Regulate Organ-Specific Light Induction of <i>SAUR</i> Genes to Modulate Cotyledon Opening during De-Etiolation in Arabidopsis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Male weanling Wistar rats from the Animal Facility at the Center for Experimental and Applied Pathology were divided into 4 groups and fed the following diets: 1) choline-deficient diet with VO [corn and hydrogenated oils) as lipids (CDVO); 2) choline-supplemented diet with VO as lipids (CSVO); 3) choline-deficient diet with MO as lipid (CDMO); and 4) choline-supplemented diet with MO as lipid (CSMO). Authors have adhered to appropriate NIH Guide for the Care and Use of Laboratory Animals. It is known that female rats are more resistant than male rats to AKI. Animals were sacrificed after receiving the experimental diets for 6 days. The left kidney was fixed in formaldehyde-buffer and stained with hematoxiline-eosin for histopathological analysis. The right kidney was cryopreserved for microarray analysis. Cryopreserved kidney was wrapped with aluminum foil and broken with a hammer previously wrapped with tape paper on a counter covered in aluminum. The pieces of the kidney were located in a mortar with liquid nitrogen to keep cryopreservation and were pulverized with a pestle. Nitrogen was added as it evaporated. The tissue was broken up to be completely pulverized. Powder was placed with a spatula in a cryotube supported on a dry ice with a layer of aluminum above. Before proceeding with another sample and to avoid contamination, the mortar, the pestle and the spatula were washed with tap water, distilled water and then alcohol. The tape of the hammer, the aluminum on the counter and the latex gloves were also replaced by new ones. Total RNA was purified from 30 milligrams of frozen rat kidney pools, using RNeasy Mini Kit [Qiagen GmbH, Hilden, Germany) according to the manufacturer's instructions. The biological concentration, integrity and quality of the RNA obtained were performing using NanoDrop 2000c (Thermo Fisher Scientific, Delaware, USA) and RIN (RNA Integrity Number). Five hundred nanograms of total RNA were processed and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array (Affymetrix Inc, Singapore, Singapore), according to Ambion WT Expression Kit instructions (Ambion Inc, Texas, USA). Total RNA obtained during the tissue extraction was processed to obtain a double strand cDNA. After that we performed a in-vitro transcripition to generate antisence cRNA (aRNA). This aRNA was used to generate a single-stranded DNA (ss-DNA) using random primers and the dUTP +dNTP mix. The resulting single-stranded DNA (ss-DNA) containing the unnatural uracilbase is then treated with Uracil DNA Glycosylase, which specifically removes the uracilresidue from the ss-DNA molecules. In the same reaction, the APE 1 enzyme then cleaves the phosphodiester backbone where the base is missing, leaving a 3-hydroxyland a 5-deoxyribose phosphate terminus. Before this prosses, shorts ss-DNA fragments were labeled by terminal deoxynucleotidyl transferase (TdT) that covalently linked the 3-hydrosyl phosphate terminus whit Biotin Allonamide Triphosphate. The GeneChip Rat Gene 1.0 ST Array enables whole-genome, gene-level expression studies for well-characterized genes. It is a single GeneChip-brand array comprised of more than 722 254 unique 25-mer oligonucleotide features accounting for more than 27 342 gene-level probe sets. Results were scanned with GeneChip Scanner 3000 7G (Affymetrix Inc, Tokyo, Japan), and normalized by RMA algorithm using Affymetrix Expression Console Software. In addition, call values were retrieved by MAS5 algorithm, and only genes with a p (present) call value were used in the analysis. Differentially expressed genes were identified using limma (www.bioconductor.org) and p adjusted values and absolute log fold change greater than 1.5 were used for gene selection.
Publication Title
Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 322 Downloadable Samples
- IlluminaHiSeq2000
Description
We report the global pattern of ileal gene expression in a cohort of 359 treatment-naïve pediatric Crohn Disease, Ulcerative Colitis patients and controls. We focus on genes with consistent altered expression in inflamed and unaffected ileum of CD [ileal-involved CD (iCD) and non-invloved ileal CD (cCD)], but not in the ileum of ulcerative colitis or control. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents aged less than 17 years, who presented with IBD-like symptoms. All patients underwent baseline colonoscopy and histological characterization; non-IBD controls were those with suspected IBD, but with no microscopic or macroscopic inflammation and normal radiographic, endoscopic, and histologic findings. Biopsies were stored at -80 degrees.
Publication Title
Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis.
Sample Metadata Fields
No sample metadata fields
View Samples