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SRP056404
Homo sapiens
5 Downloadable Samples
IlluminaHiSeq2500
Description
Periodontitis affects 47.1% of adult population in the U.S. Porphyromonas gingivalis is an opportunistic oral pathogen that colonizes the oral mucosa, invades myeloid dendritic cells and accesses the bloodstream, brain, placenta and other organs in human with periodontitis. Periodontitis also sustains a chronic long-term pro-inflammatory immune disorder, potentially contributing to other systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. However, the role of P. gingivalis minor and major fimbriae in DC-SIGN-TLR2 crosstalk during traverses from oral mucosa to these distant sites and its influence on survival of P. gingivalis within DCs and its immune-mechanism involve at molecular/transcriptome level has not been examined. In this study to address the role of fimbriae we utilized defined bacterial mutants that solely express minor fimbriae (Mfa1+Pg), major fimbriae (FimA+Pg) or are deficient in both fimbriae (MFB) and compared with un-infected control. P. gingivalis strains were maintained anaerobically (10% H2, 10% CO2, and 80% N2) in a Forma Scientific anaerobic system glove box model 1025/1029 at 37°C in Difco anaerobe broth MIC. Mutant strains were maintained using erythromycin (5 µg/ml) for mutant Mfa1+Pg, tetracycline (2 µg/ml) for mutant FimA+Pg and both erythromycin and tetracycline for double fimbriae mutant MFB. Bacterial suspensions were washed five times in PBS and re-suspended for spectrophotometer reading at OD 660 nm of 0.11, which previously determined to be equal to 5 x 107 CFU. For bacterial CFSE staining, the suspension were washed (3 times) and re-suspended in 5 µM of CFSE in PBS. The bacteria were incubated for 30 min at 37°C in the dark. MoDCs were pulsed with Pg381, Mfa1+Pg, FimA+Pg and MFB at 10 MOI and incubated with the MoDCs for 12 hours and each experimental condition was performed in triplicate. Overall design: To facilitate our understanding on host immunity and defense mechanism of this pathogen, here we used the Illumina High-throughput RNA-seq transcriptome profiling to investigate the myeloid dendritic cells response to oral Amphibiont (1. Pg381, 2. Mfa1+Pg, 3. FimA+Pg, 4. MFB and 5. Un-infected control group).
Publication Title
Oral Pathobiont Activates Anti-Apoptotic Pathway, Promoting both Immune Suppression and Oncogenic Cell Proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cells intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer.
Publication Title
The metabolic regulator ERRα, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes.
Publication Title
Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
Profiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type. Overall design: Profiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type.
Publication Title
An autofluorescence-based method for the isolation of highly purified ventricular cardiomyocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TGF-beta3 produced by developing Th17 cells induces highly pathogenic T cells that are functionally and molecularly distinct from TGF-beta1-induced Th17 cells. The microarray data represent a distinct molecular signature for pathogenic versus non-pathogenic Th17 cells.
Publication Title
Induction and molecular signature of pathogenic TH17 cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000, NextSeq 500
Description
Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC) – 5-mC's oxidation product – is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern. We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells. We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease Overall design: Profiling of the transcriptome of embryonic, neonatal, adult, 1 week hypertrophic cardiomyocytes, sh-control and sh-TET2 cardiomyocytes. Two biological replicates were profiled for each cell type.
Publication Title
DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide gene expression analysis on tibialis anterior muscle from 2-month-old nebulin SH3 domain deleted (NebSH3) mice compared to wildtype.
Publication Title
The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Illumina HiSeq 2500
Description
Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the transcripitonal profile of EEDnull, EloAnull, EloA mutant, and parental mouse embryonic stem cells by RNAseq. Please note that the .bw processed data file was generated from the *mESC replicate samples together and linked to the corresponding *rep1 sample records.
Publication Title
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the nascent transcripiton profile of mES cells by adding 5-Bromouridine (BrU) to the media for 10 min. Following RNA isolation, BrU-labelled nascent RNA species were affinity purified using BrdU antibody and sequenced after library preparation. Please note that each .bw file was generated from two replicate samples together and linked to the corresponding *rep1 sample records.
Publication Title
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 24 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Deciphering gene regulatory mechanisms through the analysis of high-throughput expression data is a challenging computational problem. Previous computational studies have used large expression datasets in order to resolve fine patterns of coexpression, producing clusters or modules of potentially coregulated genes. These methods typically examine promoter sequence information, such as DNA motifs or transcription factor occupancy data, in a separate step after clustering. We needed an alternative and more integrative approach to study the oxygen regulatory network in Saccharomyces cerevisiae using a small dataset of perturbation experiments. Mechanisms of oxygen sensing and regulation underlie many physiological and pathological processes, and only a handful of oxygen regulators have been identified in previous studies. We used a new machine learning algorithm called MEDUSA to uncover detailed information about the oxygen regulatory network using genome-wide expression changes in response to perturbations in the levels of oxygen, heme, Hap1, and Co2+. MEDUSA integrates mRNA expression, promoter sequence, and ChIP-chip occupancy data to learn a model that accurately predicts the differential expression of target genes in held-out data. We used a novel margin-based score to extract significant condition-specific regulators and assemble a global map of the oxygen sensing and regulatory network. This network includes both known oxygen and heme regulators, such as Hap1, Mga2, Hap4, and Upc2, as well as many new candidate regulators. MEDUSA also identified many DNA motifs that are consistent with previous experimentally identified transcription factor binding sites. Because MEDUSA's regulatory program associates regulators to target genes through their promoter sequences, we directly tested the predicted regulators for OLE1, a gene specifically induced under hypoxia, by experimental analysis of the activity of its promoter. In each case, deletion of the candidate regulator resulted in the predicted effect on promoter activity, confirming that several novel regulators identified by MEDUSA are indeed involved in oxygen regulation. MEDUSA can reveal important information from a small dataset and generate testable hypotheses for further experimental analysis.
Publication Title
A predictive model of the oxygen and heme regulatory network in yeast.
Sample Metadata Fields
No sample metadata fields
View Samples