PURPOSE: Hyperoxia is toxic to photoreceptors, and this toxicity may be important in the progress of retinal dystrophies. This microarray study examines gene expression induced in the C57BL/6J mouse retina by hyperoxia over the 14-day period during which photoreceptors first resist, then succumb to, hyperoxia. METHODS: Young adult C57BL/6J mice were exposed to hyperoxia (75% oxygen) for up to 14 days. On day 0 (control), day 3, day 7, and day 14, retinal RNA was extracted and processed on Affymetrix GeneChip Mouse Genome 430 2.0 arrays. Microarray data were analyzed using GCOS Version 1.4 and GeneSpring Version 7.3.1. RESULTS: The overall numbers of hyperoxia-regulated genes increased monotonically with exposure. Within that increase, however, a distinctive temporal pattern was apparent. At 3 days exposure, there was prominent upregulation of genes associated with neuroprotection. By day 14, these early-responsive genes were downregulated, and genes related to cell death were strongly expressed. At day 7, the regulation of these genes was mixed, indicating a possible transition period from stability at day 3 to degeneration at day 14. CONCLUSIONS: Microarray analysis of the response of the retina to prolonged hyperoxia demonstrated a temporal pattern involving early neuroprotection and later cell death, and provided insight into the mechanisms involved in the two phases of response. As hyperoxia is a consistent feature of the late stages of photoreceptor degenerations, understanding the mechanisms of oxygen toxicity may be important therapeutically.
Gene regulation induced in the C57BL/6J mouse retina by hyperoxia: a temporal microarray study.
Specimen part
View SamplesPurpose: In the C57BL/6J mouse retina, hyperoxia-induced degeneration of photoreceptors shows strong regional variation, beginning at a locus ~0.5mm inferior to the optic disc. To identify gene expression differences that might underlie this variability in vulnerability, we have used microarray techniques to describe regional (superior-inferior) variations in gene expression in the retina.
Differential gene expression in mouse retina related to regional differences in vulnerability to hyperoxia.
Specimen part, Treatment
View SamplesThe retinas of simian primates include a specialized, cone-rich, macula which regards the central visual field and mediates high acuity and colour vision. A prominent feature of the macula is the fovea centralis - a 1 mm-wide, avascular depression in the inner retinal surface that corresponds with a local absence of rods and a peak spatial density of cones in the outer photoreceptor layer. The arrangement of macular photoreceptors, and their specialized midget circuits, are the neural substrate for high resolution vision in primates. Macular-specific photoreceptor loss and abnormal blood vessel growth within the macula are the major causes of untreatable vision loss worldwide. However, the genes that regulate specialization of the macula, and the causes of its vulnerability to degeneration, remain obscure. Microarrays were used to compare gene expression between macula and non-macular regions during a critical phase of human retinal vascular development.
Differential expression of anti-angiogenic factors and guidance genes in the developing macula.
Specimen part
View SamplesLow-level infection is believed to play a role in the degradation of the outer blood retinal barrier, which is composed of retinal pigment epithelial (RPE) cells.
Microarray analysis of gene expression in West Nile virus-infected human retinal pigment epithelium.
Sex, Specimen part, Disease, Disease stage, Cell line
View SamplesIn fibroblasts, p65-dependent genes can be sub-divided, depending on whether they are Trap-80-dependent or -independent. To examine the generality of this grouping, we performed a microarray analysis of wild-type and Trap-80 knock-down fibroblasts, before and after stimulation of NF-kappaB activity using TNF-alpha.
Two modes of transcriptional activation at native promoters by NF-kappaB p65.
No sample metadata fields
View SamplesAim: To identify the genes and non-coding RNAs (ncRNAs) involved in the neuroprotective actions of a dietary anti-oxidant (saffron) and of photobiomodulation.
Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina.
Specimen part
View SamplesThe histological grade of carcinomas describes the ability of tumor cells to organize differentiated epithelial structures and has prognostic impact. Molecular control of differentiation in normal and cancer cells relies on lineage-determining transcription factors (TFs) that activate the repertoire of cis-regulatory elements controlling cell type-specific transcriptional outputs. TF recruitment to cognate genomic DNA binding sites results in the deposition of histone marks characteristic of enhancers and other cis-regulatory elements. Here we integrated transcriptomics and genome-wide analysis of chromatin marks in human pancreatic ductal adenocarcinoma (PDAC) cells of different grade to identify first, and then experimentally validate the sequence-specific TFs controlling grade-specific gene expression. We identified a core set of TFs with a pervasive binding to the enhancer repertoire characteristic of differentiated PDACs and controlling different modules of the epithelial gene expression program. Defining the regulatory networks that control the maintenance of epithelial differentiation of PDAC cells will help determine the molecular basis of PDAC heterogeneity and progression. Overall design: Poly(A) fraction of the total RNA from human pancreatic ductal adenocarcinoma cell lines was extracted and subjected to by multiparallel sequencing. Experiments were carried out in unmodified cells in duplicate, genome edited clonal CFPAC1 cells (2 KLF5-deleted CRISPR-Cas9 clones, 3 ELF3-deleted CRISPR-Cas9 clones and 2 wt clones) and CFPAC1 cells ectopically expressing ZEB1 or empty vector control (in duplicate).
Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer.
No sample metadata fields
View SamplesThe M1 and the M2 macrophage polarization programs (activated by IFN? and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFN? and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFN?, their coexistence with binding sites for some auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation and the starting point for understanding macrophage responses in complex environmental conditions Overall design: Analysis of transcriptional and epigenomic changes in mouse macrophages stimulated with different cytokines or their combinations
Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Specimen part, Treatment
View SamplesHistone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS)
The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis.
Specimen part, Treatment
View Samples