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GSE146615
Homo sapiens
144 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential response in gene expression to high glucose in lymphoblastoid cell lines derived from matched type 1 diabetic individuals with and without retinopathy. Those genes exhibiting the largest difference in glucose response between diabetic subjects with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a meta-genome-wide association study. All genetic variants associated with gene expression (expression QTLs; eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the glucose response gene eQTLs among small association p-values for diabetic retinopathy. Among these, we identified FLCN as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose is greater in individuals with diabetic retinopathy compared to diabetic individuals without retinopathy. Three large, independent cohorts of diabetic individuals revealed an enhanced association of FLCN eQTL to diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy in diabetic individuals. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene in diabetic retinopathy.
Publication Title
Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Noroviruses have been widely recognized for their importance as causative agents of non-bacterial gastroenteritis. Mouse norovirus is the only representative of the norovirus genus, family Caliciviridae, able to grow in cell culture. The aim of this study is to describe the differences in the expression profiles of MNV-1 and mock-infected macrophages (RAW 264.7 cells), in order to better understand the response of the host cell to norovirus infection.
Publication Title
Apoptosis in murine norovirus-infected RAW264.7 cells is associated with downregulation of survivin.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Insulators delimit independent transcriptional domains within genomes by constraining enhancer and silencer action. These transcriptional effects depend upon DNA recognition by insulator binding proteins that recruit partners that protect against inappropriate long range modulation of non-target promoters. Insulator binding proteins are broadly expressed during development, with largely constitutive binding to thousands of genomic sites. Yet, tissue-specific transcriptional changes result from the loss of individual insulator binding proteins. To understand the molecular basis for such effects, we are studying the classic Drosophila insulator protein Suppressor of Hairy-wing [Su(Hw)]. Genetic studies show that loss of this broadly expressed insulator protein prevents oocyte development. To determine the basis for the block in oogenesis, we coupled transcriptional analyses in su(Hw) mutant ovaries with genome-wide definition of Su(Hw) binding in this tissue. These studies identified 71 direct targets of Su(Hw) regulation, with nearly 70% of these genes showing increased RNA accumulation when Su(Hw) is lost. Surprisingly, derepressed Su(Hw) target genes correspond to genes normally highly expressed in neural tissues, suggesting that Su(Hw) has a critical role in silencing neural genes in the ovary. Support for this postulate was obtained by genetic studies. We found that oocyte production was restored in su(Hw) mutant females that carry a deletion of one allele of the elav family RNA binding protein 9 (Rbp9) gene. These su(Hw) null oocytes can be fertilized, with evidence that embryos lacking Su(Hw) show compromised development. Our studies extend the known transcriptional activities of Su(Hw), indicating that Su(Hw) can function as an insulator, activator and repressor, the latter function being essential for oogenesis. These findings highlight that insulator proteins are versatile transcriptional regulatory proteins, suggesting that tissue specific contributions to transcription result from direct regulation of individual genes.
Publication Title
The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Suppressor of Hairy-wing [Su(Hw)] is a multi-zinc finger DNA binding factor required for gypsy insulator function and female germline development in Drosophila. The enhancer-blocking and barrier functions of the gypsy retrotransposon involve Su(Hw) binding to twelve clustered Su(Hw) binding sites (SBSs) and recruitment of the Centrosomal Protein of 190 kD (CP190) and Modifier of mdg4 67.2 kD isoform (Mod67.2) insulator proteins. In contrast, the Su(Hw) germline function involves binding to non-clustered genomic SBSs and does not require CP190 or Mod67.2. Here, we use genome-wide expression analyses in the ovary to identify the first Su(Hw) regulated target genes.
Publication Title
The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis, however stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, we sought to identify molecular markers that could distinguish tumor cells that had completed the EMT:MET cycle in the hopes of identifying and targeting unique aspects of metastatic tumor outgrowth.Therefore, normal murine mammary gland (NMumG) cells transformed by overexpression of EGFR (NME) cells were cultured in the presence of TGF-beta1 (5 ng/ml) for 4 weeks, at which point TGF-beta1 supplementation was discontinued and the cells were allowed to recover for an additional 4 weeks (Post-TGF-Rec). Total RNA was prepared from unstimulated cells (Pre-TGF) of similar passage and compared by microarray analysis.
Publication Title
Fibroblast growth factor receptor splice variants are stable markers of oncogenic transforming growth factor β1 signaling in metastatic breast cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
Illumina HiSeq 2500
Description
To follow the changes in the transcriptional programs accompanying the specification of the adult ISCs we sequenced whole transcriptomes of embryonic intestinal epithelium progenitors (at E11.5 and E12.5) and adult ISCs. EpCAM positive embryonic gut epithelium was isolated from dissected small intestines using fluorescence activated cell sorting (FACS). Adult ISCs were purified on the basis of GFP fluorescence from crypts of Lgr5GFP-Cre-ERT mice (Barker et al. 2007) Double positive adlut ISCs were isolated by FACS based on GFP and tdTomato fluorescence. Overall design: Intestinal epithelial cells from two embryonic stages (E11.5 and E13.5), mesenchymal (E11.5) and adult Lgr5+ ISCs were used. For embryonic stages biological triplicates were analysed. For the adult ISCs either 4 biological replicates ot duplicates were analysed.
Publication Title
Id2 controls specification of Lgr5<sup>+</sup> intestinal stem cell progenitors during gut development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
LEM Domain proteins are key components of the nuclear lamina. Mutations in LEM-D proteins cause dystrophic diseases associated with compromised adult stem cells, yet it remains unclear how LEM-D proteins support stem cell function. Studies described here use the homologue of the LEM-D protein emerin in Drosophila, Otefin (Ote) as a model to understand LEM-D protein function in adult stem cells. Loss of Ote causes female sterility due to a complex germline stem cell (GSC) phenotype that includes both an early block in germline differentiation followed by GSC death. In vivo cell cycle analysis revealed that ote mutant GSCs display a lengthened S phase.We find that loss of the DNA Damage Response (DDR) Chk2 is able to not only rescue the lengthened S phase, but also GSC death and the block in germline differentiation. Activation of detrimental checkpoint in absence of Ote is conserved in both male and female GSCs and surprisingly occurs independent of detectable canonical DDR triggers, including transposon de-repression and DNA damage. Two defects were found to occur upstream of Chk2 activation: nuclear lamina morphological defects and altered heterochromatin organization. Together, our data identify the primary cause for a compromised adult stem cell population in the absence of a LEM-D protein.
Publication Title
Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here we report the characterization of a novel role for the retinoblastoma protein (pRb) as a regulator of osteoblast adhesion. Abrogation of pRb in osteoblasts resulted in aberrant cadherin expression and loss of adherens junctions. This produced defects suggestive of a transformed phenotype such as impaired cell-to-cell adhesion, loss of contact-dependent growth arrest, and the capacity to evade anoikis. This also resulted in profound abnormalities in bone structure. Consistent with this, microarray analyses showed that pRb regulates a wide repertoire of osteoblast cell adhesion genes. In addition, pRb loss also resulted in altered expression and function of several known regulators of cellular adhesion and adherens junction assembly, such as the Rho GTPase Rac1 and the merlin tumor suppressor. Taken together, our results show that pRb controls cell adhesion by regulating the expression and adherens junction components and by regulating the function of molecules involved in adherens junction assembly and stability.
Publication Title
A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation.
Sample Metadata Fields
Specimen part
View Samples- Citrus sinensis
- 6 Downloadable Samples
- Affymetrix Citrus Genome Array (citrus)
Description
We used this microarray data to survey the differentially expressed genes in sweet orange by comparing leaves challenged with X. citri ssp. citri (Xcc) strain 306 with the pthA4 gene and leaves challenged with mutant Xcc306pthA4 without the pthA4 gene 120 hours after inoculation. The deletion of the pthA4 gene reduced the virulence of Xcc306, and eliminated pustule formation. The gene expression changes after inoculation of these two strains represent PthA4-mediated molecular events in a susceptible reaction.
Publication Title
Lateral organ boundaries 1 is a disease susceptibility gene for citrus bacterial canker disease.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Pseudomonas aeruginosa
- 4 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P.aeruginosa in naturally occurring concentrations. This catabolite, 4-methylenebut-2-en-4-olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P.aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities.
Publication Title
Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response.
Sample Metadata Fields
Compound
View Samples