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GSE8083
Pseudomonas aeruginosa
5 Downloadable Samples
Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
b-Oxidative enzymes for fatty acid degradation (Fad) of long-chain fatty acid (LCFA), a component of lung surfactant phosphatidylcholine, are induced in vivo during lung infection in cystic fibrosis patients, which could contribute to nutrient acquisition and pathogenesis of Pseudomonas aeruginosa. In addition, fatty acid biosynthesis (Fab) is essential for the syntheses of two virulence controlling acylated-homoserine-lactone molecules in this organism. We mapped the promoter regions of the fadBA5-operon (PA3014 and PA3013) and a fadE homologue (PA2815) involved in Fad and the fabAB-operon involved in Fab. Focusing on the transposon mutagenesis of strain PAO1 carrying the PfadBA5-lacZ fusion, we identified a regulator for the fadBA5-operon to be PsrA (PA3006). Transcriptome analysis of the DpsrA mutant indicates its importance in regulating b-oxidative enzymes, which confirms a previous proteomic study. We further showed that induction of the fadBA-operon responds to LCFA signals, and this induction requires the presence of PsrA, suggesting that PsrA binds to LCFA to derepress fadBA5. Electrophoresis mobility shift assay indicate specific binding of PsrA to the fadBA5-promoter region. This binding is disrupted by specific LCFA (C18:1D9, C16:0, and to a lesser extent C14:0), but not by the first intermediate of b-oxidation, acyl-CoA. We proposed that PsrA is a Fad-regulator that binds and responds to LCFA signals in Pseudomonas aeruginosa.
Publication Title
The Pseudomonas aeruginosa PsrA responds to long-chain fatty acid signals to regulate the fadBA5 beta-oxidation operon.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 14 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
One of the hallmarks of Pseudomonas aeruginosa cystic fibrosis (CF) infection is very high-cell-density (HCD) replication in the lung, allowing this bacterium to induce virulence controlled by HCD quorum-sensing systems. However, the nutrient sources sustaining HCD replication in this chronic infection is largely unknown. Hence, understanding the nutrient factors contributing to HCD in the CF lung will yield new insights into the 'metabolic pathogenicity' and potential treatment of CF infections caused by P. aeruginosa. Herein, we performed microarray studies of P. aeruginosa directly isolated from the CF lung to demonstrate its metabolic capability and virulence in vivo. Our in vivo microarray data, confirmed by real-time reverse-transcription-PCR, indicated P. aeruginosa expressed several genes for virulence, drug-resistance, and utilization of multiple nutrient sources (lung surfactant lipids and amino acids) contributing to HCD replication. The data also indicates deregulation of several pathways, suggesting in vivo evolution by deregulation of a large portion of the transcriptome during chronic CF infection. To our knowledge, this is the first in vivo transcriptome of P. aeruginosa in a natural CF infection, and it indicates several important aspects of pathogenesis, drug-resistance, and nutrient-utilization never before observed in vivo.
Publication Title
In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 332 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs.
Publication Title
Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors ß-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of ß-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds ß-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. Overall design: RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
Publication Title
Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
FACS sorted TPCs (CD24HighCD44LowEpCAMHigh) and non-TPCs (CD24Low, CD24HighCD44High, and CD24HighCD44LowEpCAMLow) from mouse primary SCLC tumors
Publication Title
Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation. Overall design: RNA-seq to examine RNA editing in Fragile X patients
Publication Title
Widespread RNA editing dysregulation in brains from autistic individuals.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Subject
View Samples- Escherichia coli str. k-12 substr. mg1655
- 14 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcription profiling of wild type, relA-, and relA-spoT-, crp-, dksA-, rpoS-, lrp- mutant strains of E. coli starved for isoleucine
Publication Title
The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Brown adipose tissue is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs as essential regulators of brown adipocyte differentiation, but it remains unknown whether microRNAs are required for the feature maintenance of mature brown adipocytes. To address this question, we ablated Dgcr8, a key regulator of the microRNA biogenesis pathway, in mature brown as well as white adipocytes. The adipose tissue -specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat, and the mice were intolerant to cold exposure. In vitro primary brown adipocyte cultures confirmed that microRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that microRNAs are essential for the browning of subcutaneous white adipocyte both in vitro and in vivo. Using this animal model, we performed microRNA expression profiling analysis and identified a set of BAT-specific microRNAs that are up-regulated during brown adipocyte differentiation and enriched in brown fat compared to other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of microRNAs in the maintenance as well as the differentiation of brown adipocytes. Overall design: TotalRNAs were extracted using a Qiagen kit, and 5 µg of total RNAs for each sample were used to prepare the mRNA- Seq library according to the manufacturer’s instruction (NEB). cDNA libraries were prepared and sequenced by Hi-seq in Whitehead Genome Core. 2 replicates of each treatment were analyzed.
Publication Title
MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
Purpose: 1. Bulk-RNA-Seq was performed to identify tancytye-enriched genes. 2. scRNA-Seq was performed to profile hypothalamic cells following leptin treatment Conclusions: Leptin receptor expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms. Overall design: Methods 1 (Bulk-RNA-Seq). Flow-sorted RNA samples from Rax-EGFP BAC transgenic mice were sent to the Deep Sequencing and Microarray Core (Johns Hopkins University) for library preparation and sequencing. Briefly, polyadenylated RNA was purified from the total RNA samples using Oligo dT conjugated magnetic beads and prepared for single-end sequencing according to the Illumina TruSeq RNA Sample Preparation Kit v2 (# RS-122-2001, Illumina). The libraries were sequenced for paired-end 75 cycles using the TruSeq SBS kit on NextSeq 500 system. Filtered sequencing reads were mapped to the mouse reference genome (mm10) using TopHat. FPKM value for each gene was estimated using Cufflink. Methods 2 (scRNA-Seq). Mice brain coronal slices (aCSF- or leptin-infused) were dissociated using Act-Seq protocol and re-suspended cells were loaded into V2 10x Genomics Chromium Single Cell system, and libraries were sequenced on Illumina NextSeq with ~150 million reads per library. Sequencing results were processed 10x Genomics pipeline. Seurat V2 was used to perform downstream analysis following the standard pipeline using cells with more than 500 genes and 1000 UMI counts.
Publication Title
Tanycyte-Independent Control of Hypothalamic Leptin Signaling.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
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