This SuperSeries is composed of the SubSeries listed below.
Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts.
Sex, Treatment
View SamplesArtificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes.
Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts.
Sex, Treatment
View SamplesFoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity.
Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.
Specimen part
View SamplesMicroarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons
Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.
No sample metadata fields
View SamplesThis is the expression dataset for two studies: 1) Characterization of visceral and subcutaneous adipose tissue transcriptome and biological pathways in pregnant and non-pregnant women: Evidence for pregnancy-related regional-specific differences in adipose tissue and 2) Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: Implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Specimen part, Disease stage, Subject
View SamplesacLDL loading of mouse peritoneal macrophage is an in vitro foam cell model.
Cholesterol accumulation regulates expression of macrophage proteins implicated in proteolysis and complement activation.
No sample metadata fields
View SamplesThe mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined.
Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface.
Specimen part
View SamplesThe targeting of oncogenic ‘driver’ kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies invariably arises and is a major limitation to patient care. ROS1 fusion proteins are a recently described class of oncogenic driver, and NSCLC patients that express these fusions generally respond well to ROS1-targeted therapy. In this study, we sought to determine mechanisms of acquired resistance to ROS1 inhibition. To accomplish this, we generated a ROS1 inhibition-resistant derivative of the initially sensitive NSCLC cell line HCC78.
Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small cell lung cancer.
No sample metadata fields
View SamplesBackground: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDLs ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathways potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDLs major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-Ideficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
Specimen part
View SamplesChanges in the transcript profile due to ABCA1 expression in murine liver samples was evaluated in LDL receptor -/- genetic backgrounds.
ABCA1 overexpression in the liver of LDLr-KO mice leads to accumulation of pro-atherogenic lipoproteins and enhanced atherosclerosis.
Sex, Specimen part
View Samples