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GSE16970
Pseudomonas aeruginosa pao1
8 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Anticipating the risk for infectious disease during space exploration and habitation is a critical factor to ensure safety, health and performance of the crewmembers. As a ubiquitous environmental organism that is occasionally part of the human flora, Pseudomonas aeruginosa could pose a health hazard for the immuno-compromised astronauts. In order to gain insights in the behavior of P. aeruginosa in spaceflight conditions, two spaceflight-analogue culture systems, i.e. the rotating wall vessel (RWV) and the random position machine (RPM), were used. Microarray analysis of P. aeruginosa PAO1 grown in the low shear modeled microgravity (LSMMG) environment of the RWV compared to the normal gravity control (NG), revealed a regulatory role for AlgU (RpoE). Specifically, P. aeruginosa cultured in LSMMG exhibited increased alginate production and up-regulation of AlgU-controlled transcripts, including those encoding stress-related proteins. This study also shows the involvement of Hfq in the LSMMG response, consistent with its previously identified role in the Salmonella LSMMG- and spaceflight response. Furthermore, cultivation in LSMMG increased heat- and oxidative stress resistance and caused a decrease in the culture oxygen transfer rate. Interestingly, the global transcriptional response of P. aeruginosa grown in the RPM was similar to that in NG. The possible role of differences in fluid mixing between the RWV and RPM is discussed, with the overall collective data favoring the RWV as the optimal model to study the LSMMG-response of suspended cells. This study represents a first step towards the identification of specific virulence mechanisms of P. aeruginosa activated in response to spaceflight-analogue conditions, and could direct future research regarding the risk assessment and prevention of Pseudomonas infections for the crew in flight and the general public.
Publication Title
Response of Pseudomonas aeruginosa PAO1 to low shear modelled microgravity involves AlgU regulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa pao1
- 8 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Characterization of bacterial behavior in the microgravity environment of spaceflight is of importance towards risk assessment and prevention of infectious disease during long-term missions. Further, this research field unveils new insights into connections between low fluid-shear regions encountered by pathogens during their natural infection process in vivo, and bacterial virulence. This study is the first to characterize the global transcriptomic and proteomic response of an opportunistic pathogen that is actually found in the space habitat, Pseudomonas aeruginosa. Overall, P. aeruginosa responded to spaceflight conditions through differential regulation of 167 genes and 28 proteins, with Hfq identified as a global transcriptional regulator in the response to this environment. Since Hfq was also induced in spaceflight-grown Salmonella typhimurium, Hfq represents the first spaceflight-induced regulator across the bacterial species border. The major P. aeruginosa virulence-related genes induced in spaceflight conditions were the lecA and lecB lectins and the rhamnosyltransferase (rhlA), involved in the production of rhamnolipids. The transcriptional response of spaceflight-grown P. aeruginosa was compared with our previous data of this organism grown in microgravity-analogue conditions using the rotating wall vessel (RWV) bioreactor technology. Interesting similarities were observed, among others with regard to Hfq regulation and oxygen utilization. While LSMMG-grown P. aeruginosa mainly induced genes involved in microaerophilic metabolism, P. aeruginosa cultured in spaceflight adopted an anaerobic mode of growth, in which denitrification was presumably most prominent. Differences in hardware between spaceflight and LSMMG experiments, in combination with more pronounced low fluid shear and mixing in spaceflight when compared to LSMMG conditions, were hypothesized to be at the origin of these observations. Collectively, our data suggest that spaceflight conditions could induce the transition of P. aeruginosa from an opportunistic organism to potential pathogen, results that are of importance for infectious disease risk assessment and prevention, both during spaceflight missions and in the clinic.
Publication Title
Transcriptional and proteomic responses of Pseudomonas aeruginosa PAO1 to spaceflight conditions involve Hfq regulation and reveal a role for oxygen.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina Genome Analyzer
Description
Uterine double conditional inactivation of Smad2 and Smad3 in mice results in endometrial dysregulation, infertility, and uterine cancer. Smad2/3 cKO mice demonstrate abnormal expression of genes involved in inflammation, cell-cycle checkpoint, migration, steroid biosynthesis, and SMAD1/5-driven genes. We performed RNA-sequencing to identify the gene expression differences between the uterine epithelium of control and Smad2/3 cKO. To control for estrous cycle variations, the uterine epithelium was collected from mice at 0.5 dpc. Global gene expression profiles of Smad2/3 cKO versus control mice was analyzed. Our RNA sequencing analysis was performed at 6 weeks of life and already showed significant differences in migratory (Agr2,Slit2) and inflammatory (Ccl20, Crispld2) markers between Smad2/3 cKO and control mice. Overall design: Two group comparison: uterine epithelium of control and Smad2/3 cKO mice. We generated a conditional knockout of Smad2/3 in the uterus and demonstrated that Smad2/3 plays a critical role in the endometrium, with disruption resulting in pubertal-onset uterine hyperplasia and ultimately fatal uterine cancer.
Publication Title
Uterine double-conditional inactivation of <i>Smad2</i> and <i>Smad3</i> in mice causes endometrial dysregulation, infertility, and uterine cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Bone morphogenetic proteins (BMPs) are transforming growth factor (TGF) family members that regulate the post-implantation and mid-gestation stages of pregnancy. In this study we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. To understand the role of ALK3 in the luminal uterine epithelium, we obtained the gene expression profiles of isolated luminal uterine epithelium from 3.5dpc control and Alk3 cKO mice.
Publication Title
Uterine ALK3 is essential during the window of implantation.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Original patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles.
Publication Title
Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
By utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.
Publication Title
<i>Dnmt3a</i> restrains mast cell inflammatory responses.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In order to establish a list of candidate direct COUP-TFI gene targets in the inner ear, we analyzed the differential gene expression profiles of the wild-type and the COUP-TFI/ P0 inner ears.
Publication Title
Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 27 Downloadable Samples
Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2), Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The rapid development in septic patients of features of marked immunosuppression associated with increased risk of nosocomial infections and mortality represents the rational for the initiation of immune targeted treatments in sepsis. However, as there is no clinical sign of immune dysfunctions, the current challenge is to develop biomarkers that will help clinicians identify the patients that would benefit from immunotherapy and monitor its efficacy. Using an in vitro model of endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression in monocytes, we identified using gene expression profiling by microarray a panel of transcripts associated with the development of ET which expression was restored after immunostimulation with interferon-gamma (IFN-). These results were confirmed by qRT-PCR. Importantly, this short-list of markers was further evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1, CXCL5 and PID1) were differentially expressed in septic shock patients blood compared to healthy blood upon ex vivo LPS stimulation and were restored by IFN-. In this study, by combining a microarray approach in an in vitro model and a validation in clinical samples, we identified a panel of six transcripts that could be used for the identification of septic patients eligible for IFNg therapy. The potential value of these markers should now be evaluated in a larger cohort of patients. Upon favorable results, they could serve as stratification tools prior to immunostimulatory treatment and to monitor drug efficacy.
Publication Title
Identification of biomarkers of response to IFNg during endotoxin tolerance: application to septic shock.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 16 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Neural crest development is orchestrated by a complex and still poorly understood gene regulatory network. Premigratory neural crest is induced at the lateral border of the neural plate by the combined action of signaling molecules and transcription factors such as AP2, Gbx2, Pax3 and Zic1. Among them, Pax3 and Zic1 are both necessary and sufficient to trigger a complete neural crest developmental program. However, their gene targets in the neural crest regulatory network remain unknown. Here, through a transcriptome analysis of frog microdissected neural border, we identified an extended gene signature for the premigratory neural crest, and we defined novel potential members of the regulatory network. This signature includes 34 novel genes, as well as 44 known genes expressed at the neural border. Using another microarray analysis which combined Pax3 and Zic1 gain-of-function and protein translation blockade, we uncovered 25 Pax3 and Zic1 direct targets within this signature. We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b. In addition, they may modulate the transcriptional output of multiple signaling pathways involved in neural crest development (Wnt, Retinoic Acid) through the induction of key pathway regulators (Axin2 and Cyp26c1). We also found that Pax3 could maintain its own expression through a positive autoregulatory feedback loop. These hierarchical inductions, feedback loops, and pathway modulation provide novel tools to understand the neural crest induction network.
Publication Title
Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.
Sample Metadata Fields
Specimen part
View Samples