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GSE10710
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Overexpression of a caspase-resistant form of Bcl-2 (D34A) in human umbilical vein endothelial cells (EC) implanted into immunodeficient mice promotes the maturation of human EC-lined microvessels invested by vascular smooth muscle cells (VSMC) of mouse origin. In contrast, EC implants not overexpressing Bcl-2 form only simple, uncoated EC tubes. Here we compare the phenotypes of vessels formed in vivo and the transcriptomes in vitro of EC expressing different forms of Bcl-2. Wild type Bcl-2, like the caspase resistant D34A Bcl-2 mutant, is anti-apoptotic in vitro and promotes VSMC recruitment in vivo, whereas a G145E mutant that has diminished anti-apoptotic activity in vitro does not promote vessel maturation in vivo. The D34A and wild type forms of Bcl-2, but not the G145E mutant form of Bcl-2 significantly regulate RNA transcripts previously associated with EC-VSMC interactions and VSMC biology, including matrix Gla protein, insulin like growth factor binding protein (IGFBP)-2, matrix metaloproteinase-14 (MMP14), ADAM17 and Stanniocalcin-1. These effects of Bcl-2 on the transcriptome are detected in EC cultured as angiogenic 3-D tubes but are attenuated in EC cultured as 2-D monolayers. Bcl-2-regulated transcription in EC may contribute to vascular maturation, and support design of tissue engineering strategies using EC.
Publication Title
Antiapoptotic activities of bcl-2 correlate with vascular maturation and transcriptional modulation of human endothelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Luteinising hormone (LH) is a key regulator of male fertility through its effects on testosterone secretion by Leydig cells. Mice in which the LH receptor is knocked out (LuRKO) show reduced testicular size, reduced testosterone, elevated serum LH, and a spermatogenic arrest that can be rescued by administration of testosterone. This study examines the onset of spermatogenic arrest in LuRKO males using transcriptional profiling of developing mutant and control testes. We also examine the initial stages of testosterone rescue of the phenotype, in order to identify key upstream regulators of testosterone-dependent spermatogenesis.
Publication Title
Transcriptional profiling of luteinizing hormone receptor-deficient mice before and after testosterone treatment provides insight into the hormonal control of postnatal testicular development and Leydig cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Staphylococcus aureus
- 6 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and beta-lactams such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) and AbcA (6-fold). Other categories of genes such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time RT-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up- or down regulation by NorG. The norG mutant showed a twofold increase in the resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus.
Publication Title
Transcriptional profiling analysis of the global regulator NorG, a GntR-like protein of Staphylococcus aureus.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 35 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
S. aureus biofilms are associated with the organism's ability to cause disease. Biofilm associated bacteria must cope with the host's innate immune system.
Publication Title
Global transcriptome analysis of Staphylococcus aureus biofilms in response to innate immune cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis Genome Array (ag)
Description
Gene expression profiles of a single Arabidopsis genotype (Col-0) in response to isogenic Pseudomonas syringae strains expressing one of four different cloned avr genes was studied (avrRpt2, avrRpm1, avrPphB, avrRps4; responses mediated by the R genes RPS2, RPM1, RPS5 and RPS4 ).
Publication Title
Discovery of ADP-ribosylation and other plant defense pathway elements through expression profiling of four different Arabidopsis-Pseudomonas R-avr interactions.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2), Affymetrix Drosophila Genome Array (drosgenome1)
Description
To investigate the systemic molecular changes occurring as a result of Dhr96 knockdown or over-expression, a comparison between knockdown or overexpression lines and their genetic controls were performed. 0-3 day old adult males or females were reared on 3 separate batches of diet (this was the standard diet we used for culturing Drosophila melanogaster and was made up of 10L water, 100g agar (USP #7060 Bio-serve), 350g Brewers dried yeast (Sunshine Health), 300g black treacle (Lyles), 150g sucrose (Tate & Lyle), 300g Difco dextrose (Becton Dickinson), 150g cornmeal (#1151, Bioserve), 100g wheatgerm (#1659, Bioserve), 200g soya bean flour (#S9633 Sigma Aldrich), 10g methyl-4-hydroxybenzoate (#H3647 Sigma Aldrich) in 10ml ethanol, 50ml proprionic acid (#P5561 Sigma Aldrich)). Each of these 3 batches was considered to represent independent biological replication. The RNA samples were hybridized to the Affymetrix Drosophila GeneChip 2.
Publication Title
Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 14 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
To test whether other genes were being silenced in the Cyp6g1 knockdown strain due to off-target RNAi effects, and whether other gene expression changes were contributing to the altered susceptibility to imidacloprid in these knockdown flies. A comparison between w;Act5C-GAL4/CyO; UAS:RNAi_Cyp6g1Hp2/TM3Sb and the genetic control w;Act-GAL4/CyO;+/TM3Sb was performed. Ten 2-3 day old adult males or females were transferred to sugar-agar plates and then collected at various time points (0, 2, 5, 8 hours). The RNA samples for up to three independent experiments per timepoint for each genotype were then pooled, in equal concentrations, before hybridisation to the Affymetrix Drosophila GeneChip 1.
Publication Title
Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Staphylococcus aureus
- 8 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Staphylococcus aureus is a major human pathogen and resistant to numerous clinically used antibiotics. The first antibiotic developed for S. aureus infections was the nonribosomal petide secondary metabolite penicillin. We discovered cryptic nonribosomal peptide secondary metabolites, the aureusimines, made by S. aureus itself that are not antibiotics, but function as small molecule regulators of virulence factor expression. Using established rules and codes for nonribosomal peptide assembly we predicted these nonribosomal peptides, and used these predictions to identify them from S. aureus culture broths. Functional studies using global microarray and mouse bacteremia models established that the aureusimines control virulence factor expression and are necessary for productive infections. This is the first report of the aureusimines and has important implications for the treatment of drug resistant S. aureus. Targeting aureusimine synthesis may provide novel anti-infectives.
Publication Title
Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence.
Sample Metadata Fields
No sample metadata fields
View Samples