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GSE5680
Rattus norvegicus
120 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F2 rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta 2 associated with a decreased expression level of the gene encoding short-wave sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet-Biedl syndrome. These data and analytic approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease.
Publication Title
Regulation of gene expression in the mammalian eye and its relevance to eye disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We used a novel approach to study the acute effect of three physiologic stressors (active contractions, vibration, and systemic heat stress) in human skeletal muscle. Three hours after the completion of a dose of physiologic stress, we sampled the soleus (contraction and vibration) or vastus lateralis (heat) muscle and developed a unique gene expression signature for each stressor. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold change), PGC-1 (5.46 fold change), and ABRA (5.98 fold change); and repressed MSTN (0.56 fold change). Heat stress repressed PGC-1 (0.74 fold change); while vibration induced FOXK2 (2.36 fold change). Vibration similarly caused a down regulation of MSTN (0.74 fold change), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 while heat stress repressed PGC-1 (0.74 fold change) and ANKRD1 genes (0.51 fold change). These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
Publication Title
Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Exercise attenuates the development of chronic non-communicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed using a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for Metabolism (38 gene sets), Cell Cycle (36 gene sets), Disease (27 gene sets), Gene Expression and Transcription (22 gene sets), Organelle Biogenesis (4 gene sets), Cellular Response to Stimuli (8 gene sets), Immune System (8 gene sets), Vesicle Mediated Transport (4 gene sets), and Transport of Small Molecules (3 gene sets). Specific gene expression included: Oxidative catabolism of glucose including PDHB (p<0.001), PDHX (p<0.001), MPC1 (p<0.009), and MPC2 (p<0.007); Oxidative phosphorylation genes including SDHA (p<0.006), SDHB (p<0.001), NDUFB1 (p<0.002), NDUFA2 (p<0.001); Transcription Genes including PGC1α (p<0.030) and PRKAB2 (p<0.011); Hypertrophy gene MSTN (p<0.001); and the Myokine generating FNDC5 gene (p<0.008). Long-term electrically induced exercise de-methylated the major transcription factor, PGC1a. Taken together, these findings support that long term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.
Publication Title
Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [AltAnalyz probeset-to-Ensembl mapping (huex10st)
Description
Purpose: Age-related degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE)/choroid from early AMD and control maculas using exon-based arrays. Methods: Gene expression levels in nine early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using DAVID, and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. CFH genotype was also assessed and differential expression was analyzed with respect to high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Results: Seventy-five genes were identified as differentially expressed (raw p-value < 0.01; >50% fold change, mean log2 expression level in AMD or control median of all average gene expression values); however, no genes were significant (adj. p-value < 0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change < 0.5; raw p-value < 0.01), 18 genes were identified by DAVID analysis as associated with vision or neurological processes. GSEA of RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis with respect to CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p-value = 0.0008). Conclusions: GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout occurs early in the pathogenesis of AMD.
Publication Title
Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.
Publication Title
ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 4 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
RNA localization is a fundamental mechanism for controlling the spatial regulation of protein synthesis within cells, as well as differential cell fates during early development. Localized RNAs are known to control critical aspects of early Xenopus development, but few have been studied in detail. We set out to identify novel transcripts localized to the vegetal cortex of Xenopus oocytes, one of the best-studied examples of RNA localization. We identified over 400 transcripts enriched in the vegetal cortex, compared with whole oocytes. Included were many novel genes, as well as known genes not thought to undergo RNA localization. These data suggest that the role of RNA localization in early development is extensive and will provide a resource for identifying candidate regulatory genes for early developmental processes.
Publication Title
Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 82 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We extracted nascent plasma cell tumor (PCT) cells from within inflammatory granulomas (OG) isolated from intraperitoneal pristane-injected BALB/c.iMyc E mice at five different time points during tumor progression. We used laser capture micro-dissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice
Publication Title
Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
Publication Title
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The objective of the overall study was to determine the effects of oral vitamin D supplementation on alveolar macrophages from human subjects. In this substudy, subjects treated with vitamin D (intervention group) in paired analysis had small, but significant effects on immune-related differential gene expression pre versus post supplementation.
Publication Title
Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
There is a critical need in cancer therapeutics to identify targeted therapies that will improve outcomes and decrease toxicities compared to conventional, cytotoxic chemotherapy. Ewing sarcoma is a highly aggressive bone and soft tissue cancer that is caused by the EWS-FLI1 fusion protein. Although EWS-FLI1 is specific for cancer cells, and required for tumorigenesis, directly targeting this transcription factor has proven challenging. Consequently, targeting unique dependencies or key downstream mediators of EWS-FLI1 represent important alternative strategies. We used gene expression data derived from a genetically defined model of Ewing sarcoma to interrogate the Connectivity Map and identify a class of drugs, iron chelators, that downregulate a significant number of EWS-FLI1 target genes. We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. Inhibition of RNR in Ewing sarcoma cells led to apoptosis and cell death in vitro and attenuated tumor growth in vivo in a xenograft model. Additionally, we discovered that the sensitivity of Ewing sarcoma cells to inhibition or suppression of RNR is mediated, in part, by high levels of SLFN11, a protein that sensitizes cells to DNA damage. This work demonstrates a unique dependency of Ewing sarcoma cells on RNR and supports further exploration of clinically used inhibitors of RNR as a therapeutic approach in treating this cancer.
Publication Title
Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples