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Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems (T3SSs), encoded in pathogenicity islands 1 (SPI1) and 2 (SPI2), respectively. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with certain host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both T3SSs. Nothing is known about the function of this protein inside the host cells. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in epithelial cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also represses genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. Consisted with this analysis a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, reduction of cytotoxicity, cell-cell adhesion and migration capability, and increase in endocytosis.
Publication Title
Global impact of Salmonella type III secretion effector SteA on host cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Thymic lymphomas develop spontaneously in LN3 mice. As for T-ALL in general, ex vivo LN3 lymphoma cells require stromal support to remain viable in culture. We found that primary stromal cells from thymic lymphomas, but not from wild-type thymi, support ex vivo lymphoma survival. By FACS sorting stromal populations, we identified dendritic cells in the tumor microenvironment as the cells capable of supporting lymphoma survival.
Publication Title
Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples
SRP140558- Homo sapiens
- 62 Downloadable Samples
Illumina HiSeq 2500
Description
Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence. Overall design: The study design consisted of PBMC from infants (<18months, n=15 pairs) and pre-school children (2-5yrs, n=16 pairs) sampled during severe acute viral bronchiolitis (acute visit = AV) and following recovery during convalescence (convalescent visit = CV). RNA-Seq profiles were generated by sequencing llumina HiSeq2500, 50bp single-end reads, v4 chemistry. Samples were sequenced across two lanes and collapsed prior analysis.
Publication Title
Personalized Transcriptomics Reveals Heterogeneous Immunophenotypes in Children with Viral Bronchiolitis.
Sample Metadata Fields
Subject
View Samples SRP140557- Homo sapiens
- 56 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: A subset of infants are hyper-susceptible to severe/acute viral bronchiolitis (AVB), for reasons unknown. Purpose: To characterise the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airways tissues. Methods: PBMC and nasal mucosal scrapings (NMS) were obtained from Infants (<18mths) and children (1.5-5yrs) during AVB and post-convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data utilised a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis employing personalised N-of-1-pathways methodology. Results: Group-level analyses demonstrated that infant PBMC responses were dominated by monocyte-associated hyper-upregulated type I interferon signalling/pro-inflammatory pathways (drivers: TNF, IL6, TREM1, IL1B), versus a combination of inflammation (PTGER2, IL6) plus growth/repair/remodelling pathways (ERBB2, TGFB1, AREG, HGF) coupled with Th2 and NK-cell signalling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by interferon types I-III, but the magnitude of upregulation was higher in infants (range 6-48-fold) than children (5-17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and NK cell networks in children, and additionally demonstrated covert AVB response sub-phenotypes that were independent of chronological age. Conclusions: Dysregulated expression of interferon-dependent pathways following respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects appear to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence. Overall design: The study design consisted of PBMC from infants (<18months, n=15 pairs) and pre-school children (2-5yrs, n=16 pairs) sampled during severe acute viral bronchiolitis (acute visit = AV) and following recovery during convalescence (convalescent visit = CV). RNA-Seq profiles were generated by sequencing llumina HiSeq2500, 50bp single-end reads, v4 chemistry. Samples were sequenced across two lanes and collapsed prior analysis.
Publication Title
Personalized Transcriptomics Reveals Heterogeneous Immunophenotypes in Children with Viral Bronchiolitis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Using RNA-seq we identified the gene expression changes in GC B cells from LSD1 wild-type or LSD1-deficient mice immunized with T cell dependent antigens (Sheep Red Blood cells) Overall design: RNA seq of sorted GC B cell populations from 3 littermate mice per genotype (3 wild-type, 3 knockout)
Publication Title
Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
BACKGROUND & AIMS: We performed an integrated analysis to identify microRNAs (miRNAs) and mRNAs with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.
Publication Title
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
BCL6 inhibitor induces derepression of BCL6 target genes and shows a similar transcriptional program to BCL6 siRNA Overall design: Genome-wide profiling of mRNA transcript levels in human DLBCL cell line with BCL6 inhibitor and DMSO control.
Publication Title
Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Rationale: The BCL6 oncogene is constitutively activated by chromosomal translocations and amplification in ABC-DLBCLs, a class of DLBCLs that respond poorly to current therapies. Yet the role of BCL6 in maintaining these lymphomas has not been investigated. BCL6 mediates its effects by recruiting corepressors to an extended groove motif. Development of effective BCL6 inhibitors requires compounds exceeding the binding affinity of these corepressors. Objectives: To design small molecule inhibitors with superior potency vs. endogenous BCL6 ligands for unmet putative therapeutic needs such as targeting ABC-DLBCL. Findings: We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor with 10-fold greater potency than endogenous corepressors. The compound, called FX1, binds in such a way as to occupy an essential region of the BCL6 lateral groove. FX1 disrupts BCL6 repression complex formation, reactivates BCL6 target genes, and mimics the phenotype of mice engineered to express BCL6 with lateral groove mutations. This compound eradicated established DLBCLs xenografts at low doses. Most strikingly, FX1 suppressed ABC-DLBCL cells as well as primary human ABC-DLBCL specimens ex vivo. Conclusions: ABC-DLBCL is a BCL6 dependent disease that can be targeted by novel inhibitors able to exceed the binding affinity of natural BCL6 ligands. Overall design: gene expression profiles of DLBCL cases
Publication Title
Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 175 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This project is based on the hygiene hypothesis that exposure to TB provides a protective mechanism against asthma through specific cytokines and the balance of Th1, Th2 cells. Additionally, expression changes are examined in patients with and without atopy in combination with asthma and PPD status. Expression levels were evaluated in CD4+ cells isolated from peripheral blood of 30 patients. Each patient was evaluated on the entire U133 Affymetrix GeneChip set.
Publication Title
A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.
Sample Metadata Fields
No sample metadata fields
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