MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).
Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis.
Specimen part, Disease
View SamplesTo investigate whether U1C plays a role in splicing regulation in human system, we performed siRNA-mediated knockdown of U1C in HeLa cells and analyzed alternative splicing patterns by high-throughput RNA sequencing (RNAseq) Overall design: RNAseq performed with poly(A)+ selected total RNA from U1C-knockdown and control-treated HeLa cells
A novel intra-U1 snRNP cross-regulation mechanism: alternative splicing switch links U1C and U1-70K expression.
Cell line, Treatment, Subject
View SamplesWe have investigated the regulation of anchorage-independent growth (AIG) by basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) in JB6 mouse epidermal cells in the context of wound repair versus carcinogenesis responses. bFGF induces an unusually efficient but reversible AIG response, relative to TPA-induced AIG which is irreversible. Distinct global gene expression profiles are associated with anchorage-independent colonies arising from bFGF-stimulated JB6 cells, relative to colonies arising from fully tumorigenic JB6 cells (RT101), including genes exhibiting reciprocal regulation patterns. Thus, while TPA exposure results in commitment to an irreversible and tumorigenic AIG phenotype, the AIG response to bFGF is reversible with essentially complete restoration of normal cell cycle check point control following removal of bFGF from growth medium. These results are consistent with the physiological role of bFGF in promoting wound healing, and suggest that natural mechanisms exist to reverse transformative cellular phenotypes associated with carcinogenesis.
Cellular dichotomy between anchorage-independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesThe immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesUsing a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
No sample metadata fields
View SamplesBisphenol-A is a widespread endocrine disruptor chemical. In utero or perinatal exposure to bisphenol-A (BPA), leads to impaired glucose metabolism during adulthood. To investigate the consequences of the exposure to bisphenol-A during development in pancreatic beta-cell growth
Maternal Exposure to Bisphenol-A During Pregnancy Increases Pancreatic β-Cell Growth During Early Life in Male Mice Offspring.
Sex, Specimen part
View SamplesPhenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. Overall design: RNA-seq
AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.
No sample metadata fields
View SamplesBrown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21. Overall design: eight adult male C57BL6 mice were maintained at thermoneutral temperature (29C). After two weeks, a subset of four mice was placed at 4C environment temperature for 24h. RNAseq was performed on the BAT tissues of these 2 groups.
The kallikrein-kinin pathway as a mechanism for auto-control of brown adipose tissue activity.
Sex, Specimen part, Subject
View SamplesThe purpose of our study was to identify expression signatures and molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.
Sex, Specimen part
View Samples