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GSE13534
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Purpose: Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. The authors report the first study of global and ECM-focused gene transcription differentials between GFAP-negative negative lamina cribrosa (LC) cells from normal and POAG human donors. Methods: GFAP-negative LC cell lines were generated from the optic nerve tissue of three normal (n=3) and three POAG (n=3) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was carried out using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. Results: 285 genes were up regulated by greater than 1.5 fold and 413 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, SPARC, periostin, thrombospondin, CRTL-1, CTGF and collagen types I, III, V and VIII. Downregulated ECM genes in POAG included MMP-1, fibulin, decorin and tenacsin XB. All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. Conclusions: This study reports for the first time that POAG LC cells in-vitro demonstrate up regulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling and an attractive target for future therapeutic strategies in POAG.
Publication Title
Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human lamina cribrosa cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Vascular hypoperfusion is a pathological phenomenon in the glaucomatous optic nerve head. We report transcriptional responses in GFAP-negative LC cells exposed to in-vitro hypoxic stress (1%O2).
Publication Title
Hypoxia regulated gene transcription in human optic nerve lamina cribrosa cells in culture.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extra-cellular matrix (ECM) remodelling accompanies axonal damage in the lamina cribrosa (LC) of the optic nerve head in POAG. Glial cells in the lamina cribrosa may play a role in this process but the precise cellular responses to mechanical forces in this region are unknown. The authors examined global gene expression profiles in lamina cribrosa cells exposed to cyclical mechanical stretch, with an emphasis on ECM genes.
Publication Title
Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A causal role of mutations in genes encoding for multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations at the global level of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for global changes in the overall distribution of gene expression levels. For instance, in mice, we recently showed that variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in the variance in gene expression levels might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on purified RNA from peripheral blood lymphocytes of children with autism (n=82) and controls (n=64). The variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance in the overall distribution of gene expression levels. A decrease in the variance in the distribution of gene expression levels in peripheral blood lymphocytes (PBL) was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
Publication Title
Autism and increased paternal age related changes in global levels of gene expression regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Publication Title
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P. aeruginosa virulence in C. elegans. Approximately half of the hits were known antimicrobials. A large number of hits were non-antimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine anti-virulent compound, with no bacteriostatic or bacteriocidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P. aeruginosa.
Publication Title
A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Zea mays
- 19 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Aluminum toxicity is one of the major limiting factors for many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth, leading to poor water and nutrient absorption. The causes of this inhibition are still elusive, with several biochemical pathways being affected and with a significant variation between species. Most of the work done so far to investigate the genes responsible for Al tolerance used hydroponic culture. Here we evaluated plant responses using soil as substrate, which is a condition closer to the field reality.
Publication Title
Transcriptional profile of maize roots under acid soil growth.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Pseudomonas aeruginosa is a re-emerging opportunistic pathogen with broad antimicrobial resistance. We have previously reported that the major siderophore pyoverdine from this pathogen disrupts mitochondrial networks and induces a lethal hypoxic response in model host Caernorhabditis elegans. However, the mechanism of such cytotoxicity remained unclear. Here, we demonstrate that pyoverdine translocates into host cells, binding to host ferric iron sources. The reduction of host iron content disrupts mitochondrial function such as NADH oxidation and ATP production and activates mitophagy. This activates a specific immune response that is distinct from colonization-based pathogensis and exposure to downstream pyoverdine effector Exotoxin A. Host response to pyoverdine resembles that of a hypoxic crisis or iron chelator treatment. Furthermore, we demonstrate that pyoverdine is a crucial virulence factor in P. aerguinosa pathogenesis against cystic fibrosis patients; F508 mutation in human CFTR increases susceptibility to pyoverdine-mediated damage.
Publication Title
Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ikaros hypomorphic mice (IkL/L) show plasmacytoid dendritic cell (pDC) defects with an absence of pDCs in the peripheral organs and a reduction of pDCs in the bone marrow (BM). Moreover in vitro differentiation of pDC from IkL/L total BM cells is also defective.
Publication Title
Ikaros cooperates with Notch activation and antagonizes TGFβ signaling to promote pDC development.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-cat) in which high levels of active -catenin are maintained throughout T cell development. Young R26-cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age.
Publication Title
β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL.
Sample Metadata Fields
Age, Specimen part
View Samples