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SRP068163
Homo sapiens
8 Downloadable Samples
Illumina HiSeq 1500
Description
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is regulated by environmental toxicants that function as AHR agonists such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). L-Type Amino Acid Transporter 1 (LAT1) is a leucine uptake transporter that is overexpressed in cancer. The regulation of LAT1 by AHR in MCF-7 and MDA-MB-231 breast cancer cells (BCCs) was investigated in this report. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and molecular transport. Overlapping the TCDD-RNA-Seq dataset in this report with a published TCDD-ChIP-seq dataset identified that LAT1 was a direct TCDD/AHR gene target. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed that TCDD-stimulated increases in LAT1 mRNA and protein required AHR. TCDD-stimulated increases in LAT1 mRNA was also inhibited by the AHR antagonist CH-223191. Upregulation of LAT1 by TCDD coincided with increases in leucine uptake by MCF-7 cells in response to TCDD. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays revealed increases in AHR, AHR nuclear translocator (ARNT) and p300 binding and histone H3 acetylation at an AHR binding site in the LAT1 gene in response to TCDD. In MDA-MB-231 cells, which exhibit high levels of endogenous AHR activity, the levels of endogenous LAT1 mRNA and protein were reduced in response to knockdown of AHR with AHR-siRNA. The regulation of LAT1 by AHR stimulated MDA-MB-231 proliferation. Collectively, these findings have provided a deeper mechanistic understanding of extrinsic and intrinsic regulation of LAT1 by AHR. Overall design: Expression profiling of four replicates of MCF-7 cells treated with 10nM TCDD were compared to expression profiles of four control replicates of MCF-7 cells treated with DMSO by RNA-Seq
Publication Title
Aryl hydrocarbon receptor (AHR) regulation of L-Type Amino Acid Transporter 1 (LAT-1) expression in MCF-7 and MDA-MB-231 breast cancer cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of alterations in the hippocampus transcriptome caused by deletion of Mitogen Stress activated Kinase 1 (MSK1).
Publication Title
Mitogen- and Stress-Activated Protein Kinase 1 Regulates Status Epilepticus-Evoked Cell Death in the Hippocampus.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 18 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Most CF patients acquire unique P. aeruginosa strains from the environment; however clonal strains have been identified in CF communities in several countries. Two clonal strains infect 10% to 40% of patients in three CF clinics in mainland eastern Australia. The expression profiles of four planktonically-grown isolates of one Australian clonal strain (AES-1), and four nonclonal CF P. aeruginosa isolates were compared to each other and to the reference strain PAO1 using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating the enhanced infectivity of AES-1. The isolates were subsequently grown as 3-day old biofilms and similarly extracted for RNA and compared as above. Data analysis was carried out using BIOCONDUCTOR software.
Publication Title
Gene expression characteristics of a cystic fibrosis epidemic strain of Pseudomonas aeruginosa during biofilm and planktonic growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. Overall design: 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.
Publication Title
Significant association between host transcriptome-derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina Genome Analyzer II
Description
miR-132 and miR-212 are structurally-related microRNAs that have been found to exert powerful modulatory effects within the central nervous system (CNS). Notably, these microRNAs are tandomly processed from the same non-coding transcript, and share a common seed sequence: thus it has been difficult to assess the distinct contribution of each microRNA to gene expression within the CNS. Here, we employed a combination of conditional knockout and transgenic mouse models to examine the contribution of the miR-132/212 gene locus to learning and memory, and then to assess the distinct effects that each microRNA has on hippocampal gene expression. Using a conditional deletion approach, we show that miR-132/212 double knockout mice exhibit significant cognitive deficits in spatial memory, recognition memory, and in tests of novel object recognition. Next, we utilized transgenic miR-132 and miR-212 overexpression mouse lines and the miR-132/212 double knockout line explore the distinct effects of these two miRNAs on the transcriptional profile of the hippocampus. Illumina sequencing revealed that miR-132/212 deletion increased the expression of 1,138 genes; Venn analysis showed that 96 of these genes were also downregulated in mice overexpressing miR-132. Of the 58 genes that were decreased in animals overexpressing miR-212, only four of them were also increased in the knockout line. Functional gene ontology analysis of downregulated genes revealed significant enrichment of genes related to synaptic transmission, neuronal proliferation, and morphogenesis, processes known for their roles in learning, and memory formation. These data, coupled with previous studies, firmly establish a role for the miR-132/212 gene locus as a key regulator of cognitive capacity. Further, although miR-132 and miR-212 share a seed sequence, these data indicate that these miRNAs do not exhibit strongly overlapping mRNA targeting profiles, thus indicating that, these two genes may function in a complex, non-redundant manner to shape the transcriptional profile of the CNS. The dysregulation of miR-132/212 expression could contribute to signaling mechanisms that are involved in an array of cognitive disorders Overall design: Hippocampal mRNA was isolated from CaMKII-Cre::miR-132/212f/f, tTA::miR132, and tTA::miR212 animals, as well as their respective nontransgenic controls. cDNA from six animals was pooled into three independent biological replicates for each. Libraries were prepared according to the Illumina TruSeqTM Sample Preparation Guide and sequenced using an Illumina Genome Analyzer II. Sequences were aligned to the UCSC mm9 reference genome using Bowtie v0.12.7 and custom R scripts. The sequence data have been submitted to the NCBI Short Read Archive with accession number in progress. Relative abundance was measured in Fragments Per Kilobase of exon per Million fragments mapped using Cufflinks v1.2.
Publication Title
Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome.
Sample Metadata Fields
Cell line, Subject
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Most CF patients acquire unique P. aeruginosa strains from the environment; however clonal strains have been identified in CF communities in several countries. Two clonal strains infect 10% to 40% of patients in three CF clinics in mainland eastern Australia. The expression profiles of four planktonically-grown isolates of one Australian clonal strain (AES-2), and four nonclonal CF P. aeruginosa isolates were compared to each other and to the reference strain PAO1 using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating the enhanced infectivity of AES-1. The isolates were subsequently grown as 3-day old biofilms and similarly extracted for RNA and compared as above. Data analysis was carried out using BIOCONDUCTOR software.
Publication Title
Transcriptome analyses and biofilm-forming characteristics of a clonal Pseudomonas aeruginosa from the cystic fibrosis lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Using complementary forms of high dimensional profiling we define differences in CD45+ cells from syngeneic mouse tumors that either grow progressively or eventually reject following immune checkpoint therapy (ICT). Unbiased assessment of gene expression of tumor infiltrating cells by single cell RNA sequencing (scRNAseq) and longitudinal assessment of cellular protein expression by mass cytometry (CyTOF) revealed significant remodeling of both the lymphoid and myeloid intratumoral compartments. Surprisingly, we observed multiple subpopulations of monocytes/macrophages distinguishable by the combinatorial presence or absence of CD206, CX3CR1, CD1d and iNOS, markers of different macrophage activation states that change over time during ICT in a manner partially dependent on IFN?. Both the CyTOF data and additional analysis of scRNAseq data support the hypothesis that macrophage polarization/activation results from effects on circulatory monocytes/early macrophages entering tumors rather than on pre-polarized mature intratumoral macrophages. Thus, ICT induces transcriptional and functional remodeling of both myeloid and lymphoid compartments. Overall design: Droplet-based 3' end massively parallel single-cell RNA sequencing was performed by encapsulating sorted live CD45+ tumor infiltrating cells into droplets and libraries were prepared using Chromium Single Cell 3' Reagent Kits v1 according to manufacturer's protocol (10x Genomics). The generated scRNAseq libraries were sequenced using an Illumina HiSeq2500.
Publication Title
High-Dimensional Analysis Delineates Myeloid and Lymphoid Compartment Remodeling during Successful Immune-Checkpoint Cancer Therapy.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aged STAT1-/- female mice spontaneously develop ERa+ PR+ mammary tumors that exhibit strikingly similar hormone-sensitivity and -dependency as human ERa+ luminal breast cancers.
Publication Title
STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The polarization of macrophages into an anti-inflammatory or regulatory phenotype plays an important role in resolving inflammation. PGE2 regulates macrophage polarization via a PKA dependent pathway. PKA phosphorylates SIKs, inhibiting their ability to phosphorylate CRTC3 in cells. This in turn allows CRTC3 to translocate to the nucleus where it acts as a co-activator with the transcription factor CREB to induce IL-10 transcription. In line with this we find that either genetic or pharmacological inhibition of SIKs mimics the effect of PGE2 on IL-10 production.
Publication Title
PGE(2) induces macrophage IL-10 production and a regulatory-like phenotype via a protein kinase A-SIK-CRTC3 pathway.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Analysis of the effects of three members of the FGF family (FGF1, FGF2 and FGF9) and bone morphogenic protein 4 (BMP4) on myelinating cultures generated from dissociated embryonic spinal cord. The results of both immediate (24 hours, T1 (24 hrs)) and long term treatments (10days, T2) give insights into the cumulative effects of sustained FGF and BMP mediated signal transduction in the pathogenesis of demyelinating diseases.
Publication Title
Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples