Fine control of macrophage activation is required to prevent inflammatory disease, particularly at barrier sites such as the lung. However, the dominant mechanisms that regulate pulmonary MFs during inflammation are currently poorly understood. Here we show that airway MFs are substantially less able to respond to the canonical type-2 cytokine IL-4, which underpins allergic disease and parasite worm infections, than lung tissue or peritoneal cavity MFs. We reveal that MF hypo-responsiveness to IL-4 is dictated by the lung environment, though independent of the host microbiota or the prominent lung extracellular matrix components surfactant protein D and mucin 5b. Rather, compared to cavity MFs, airway MFs display severely dysregulated metabolism. Strikingly, upon removal from the lung, alveolar MFs regain IL-4 responsiveness in a process dependent upon glycolysis. Thus, we propose that impaired glycolysis within the pulmonary niche is a central determinant for regulation of MF responsiveness during type-2 inflammation. Overall design: The 13 analysed samples belong to 6 different groups, each group consisted of 2 or 3 samples. The groups consist of 3 separate macrophage populations, from either control or IL-4 complex treated mice. Each individual sample was generated from 3-5 pooled biological replicate mice.
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.
Treatment, Subject
View SamplesIn fission yeast, the nuclear-localized Lsk1p-Lsc1p-Lsg1p cyclin dependent kinase complex is required for the reliable execution of cytokinesis and is also required for Ser-2 phosphorylation RNA pol II carboxy terminal domain.
Global gene expression analysis of fission yeast mutants impaired in Ser-2 phosphorylation of the RNA pol II carboxy terminal domain.
No sample metadata fields
View SamplesAnalysis of spleen samples taken throughout the acute phase of infection from mice infected with virulent P. chabaudi CB strain
Transcriptome analysis of blood and spleen in virulent and avirulent mouse malaria infection.
Sex, Specimen part, Time
View SamplesRodent malaria parasite RNA hybridized on Illumina Mouse WG-6 v2.0 Expression BeadChip
Transcriptome analysis of blood and spleen in virulent and avirulent mouse malaria infection.
Sex, Specimen part
View SamplesThis study assessed the transcriptional profile of SiHa cells. SiHa is a cervical cancer cell line with integrated HPV16, and was used as a model to study human gene expression in the context of integrated virus. Gene expression in SiHa, calculated by Cufflinks, was scored in windows around the locations of known viral integrations in patients or cell lines to determine if there was an association between gene expression and viral integration. We found that SiHa gene expression was higher near loci of integration for HPV18 vs. HPV16, cervical tissues vs. head and neck cancers, and cervical cancers vs. in vitro integrations. This study provides insight into the factors that may influence where viruses integrate in the human genome. Overall design: Gene Expression in untreated SiHa cells.
Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics.
No sample metadata fields
View SamplesBeef cow adipose tissue transcriptome
Differential transcript abundance in adipose tissue of mature beef cows during feed restriction and realimentation.
Specimen part
View SamplesMitochondrial oxidative function is tightly controlled to maintain energy homeostasis in response to nutrient and hormonal signals. An important cellular component in the energy sensing response is the target of rapamycin (TOR) kinase pathway; however whether and how mTOR controls mitochondrial oxidative activity is unknown. Here, we show that mTOR kinase activity stimulates mitochondrial gene expression and oxidative function. In skeletal muscle cells and TSC2-/- MEFs, the mTOR inhibitor rapamycin largely decreased gene expression of mitochondrial transcriptional regulators such as PGC-1alpha and the transcription factors ERRalpha and NRFs. As a consequence, mitochondrial gene expression and oxygen consumption were reduced upon mTOR inhibition. Using computational genomics, we identified the transcription factor YY1 as a common target of mTOR and PGC-1alpha that controls mitochondrial gene expression. Inhibition of mTOR resulted in a failure of YY1 to interact and be coactivated by PGC-1alpha. Notably, knock-down of YY1 in skeletal muscle cells caused a significant decrease in mRNAs of mitochondrial regulators and mitochondrial genes that resulted in a decrease in respiration. Moreover, YY1 was required for rapamycin-dependent repression of mitochondrial genes. Thus, we have identified a novel mechanism in which a nutrient sensor (mTOR) balances energy metabolism via transcriptional control of mitochondrial oxidative function. These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer.
mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
No sample metadata fields
View SamplesCraniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of isolated single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive at best. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as potential genetic biomarkers for single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Furthermore, pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only differentially regulated genes identified in a direct comparison. These results not only confirm the roles of previously reported craniosynostosis-related targets but also introduce novel genetic biomarkers and pathways that may play critical roles in its pathogenesis.
Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis.
Sex, Specimen part
View SamplesA c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rß). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients. Overall design: Wild-type MCF-7 cells were treated with vehicle control (0.1% ethanol), E2 (10-9 mol/L) and 4-OHT (10-6 mol/L) respectively for 24 hours.
Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells.
No sample metadata fields
View SamplesThis dataset was used to establish whole blood transcriptional modules (n=260) that represent groups of coordinately expressed transcripts that exhibit altered abundance within individual datasets or across multiple datasets. This modular framework was generated to reduce the dimensionality of whole blood microarray data processed on the Illumina Beadchip platform yielding data-driven transcriptional modules with biologic meaning.
Interferon signature in the blood in inflammatory common variable immune deficiency.
Disease
View Samples