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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
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility).
Publication Title
Differential RNAs in the sperm cells of asthenozoospermic patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Overall design: RNA profiles in wild-type and Taf4-/- livers by deep sequencing
Publication Title
TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice lacking the beta 2 subunit (Chrnb2) of the neuronal nicotinic acetylcholine receptor display altered retinal waves and disorganized projections of the retinal ganglion cells to the lateral geniculate nucleus (LGN). mRNA populations from retinas and LGN from Chrnb2-/-and wild type (C57BL/6J) mice were compared at 4 days postnatal, when RGC segregation to the LGN begins in WT mice. Retinal mRNAs were also compared at adulthood.
Publication Title
Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman), Infinium MethylationEPIC
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The adipose tissue is an endocrine regulator and a risk factor for atherosclerosis and cardiovascular disease when by excessive accumulation induces obesity. Although the adipose tissue is also a reservoir for stem cells (ASC) their function and stemcellness has been questioned. Our aim was to investigate the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT) stem cells.
Publication Title
Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 5 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particulary involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases.
Publication Title
Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcription factor induced reprogramming of one specialized cell type into another is a promising approach for regenerative medicine. However, the process still remains poorly understood, in large part because of the lack of adequate experimental models. Here we describe a robust cell reprogramming system consisting of a B cell line with an inducible form of C/EBPa that can be converted into macrophages with essentially 100% efficiency in only 2 to 3 days. The conversion involves reciprocal changes in cell surface antigen expression, increase in cell granularity and size, alterations in cellular structures, formation of membrane extensions, acquisition of phagocytic capacity and an increased inflammatory responsiveness as well as migratory activity. Analysis of the transcriptome shows complex reciprocal regulation of B cell and macrophage genes, including transcription factors required for the formation of the two lineages. The fact that the cells become irreversibly committed to a macrophage fate within 1 to 2 days after activation of C/EBPa show that they are truly reprogrammed. The system should be useful to study epigenetic and cell biological mechanisms of transcription factor induced cell reprogramming.
Publication Title
A robust and highly efficient immune cell reprogramming system.
Sample Metadata Fields
Cell line
View Samples- Sus scrofa
- 10 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The liver transcriptomes of two female groups (High and Low) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq [accn: SRA053452, subid: 86092, Bioproject: PRJNA168072]. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism.
Publication Title
Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition.
Sample Metadata Fields
Sex, Specimen part
View Samples