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SRP057134
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
Thymic antigen-presenting cells (APCs), including thymic dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs) have been described to play a critical role in thymic Treg generation. Our findings could show that both these thymic APCs can induce a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signature genes in developing Tregs when compared to splenic DCs. In order to elucidate the unique properties of thymic APCs, gene expression profiling was performed in comparison to splenic DCs. Transcriptome analysis of thymic APCs revealed differential expression of costimulatory molecules that could be involved in stable Treg generation. Importantly, both mTEC- and t-DC- induced alloantigen-specific Tregs displayed significantly higher efficacy in prolonging skin allograft acceptance when compared to alloantigen-specific Tregs generated by splenic DCs. Overall design: Thymic APCs, including mTECs and t-DCs and splenic DCs were isolated ex vivo from thymus as CD45-EpCAM+Ly51- (mTECs) and CD45+EpCAM-CD11chiLin- (t-DCs) and from spleen as CD11chiLin- (splenic DCs) (Lin is defined as CD90, CD49b, F4/80 and CD19), respectively.
Publication Title
Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression profiling was carried out on primary ovarian carcinomas from 10 patients. The primary research question is whether gene expression differs in tissues from individuals with high vs low symptoms of psychological depression.
Publication Title
Depression, social support, and beta-adrenergic transcription control in human ovarian cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Inhibition of the costimulatory CD40-CD40L receptor/ligand dyad drastically reduces atherosclerosis. However, its long-term blockage can result in immune suppression. We recently identified small molecule inhibitors that block the interaction between CD40 and TNF Receptor Associated Factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity. Here we further characterized the working mechanisms of TRAF-STOPs 6877002 and 6860766 in atherogenesis.
Publication Title
Targeting CD40-Induced TRAF6 Signaling in Macrophages Reduces Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Publication Title
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals Overall design: WGBS, RNA-seq, and microarrays were used to study epigenetics and transcriptomics human cancer isolated subcutaneous (abdominal - SA) and vieceral (omental - VA) adipocyte, peripheral blood leukocytes (PBL) and visceral adipose tissue (VAT).
Publication Title
Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
LEM Domain proteins are key components of the nuclear lamina. Mutations in LEM-D proteins cause dystrophic diseases associated with compromised adult stem cells, yet it remains unclear how LEM-D proteins support stem cell function. Studies described here use the homologue of the LEM-D protein emerin in Drosophila, Otefin (Ote) as a model to understand LEM-D protein function in adult stem cells. Loss of Ote causes female sterility due to a complex germline stem cell (GSC) phenotype that includes both an early block in germline differentiation followed by GSC death. In vivo cell cycle analysis revealed that ote mutant GSCs display a lengthened S phase.We find that loss of the DNA Damage Response (DDR) Chk2 is able to not only rescue the lengthened S phase, but also GSC death and the block in germline differentiation. Activation of detrimental checkpoint in absence of Ote is conserved in both male and female GSCs and surprisingly occurs independent of detectable canonical DDR triggers, including transposon de-repression and DNA damage. Two defects were found to occur upstream of Chk2 activation: nuclear lamina morphological defects and altered heterochromatin organization. Together, our data identify the primary cause for a compromised adult stem cell population in the absence of a LEM-D protein.
Publication Title
Nuclear lamina dysfunction triggers a germline stem cell checkpoint.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The aim of present study was to describe the genetic pathways activated during the community acquired bacterial meningitis (BM) by using genome-wide RNA expression profiling combined with functional annotation of transcriptional changes. We included 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed with GeneChip Human Gene 1.0 ST Arrays enabling the analysis of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define changed genetic networks. We also analyzed if the gene expression profile depends on the clinical course and outcome. In order to verify the genechip results, we chose ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, IL7R) and performed quantitative real-time (qRT) PCR.We identified the significant differences at p values of <0.05 in 8569 genes and after False Discovery Rate (FDR) correction, total of 5500 genes remained significant at p value of <0.01. Quantitative RT-PCR confirmed differential expression for selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in adults and in children with BM compared to the healthy controls. Gene expression profile didnt depend on the clinical outcome, but there was very strong influence by the type of the pathogen. This study demonstrates a strong functional genomic evidence of the over-active immune response during bacterial meningitis. This hyperactive response possibly explains the complicated clinical course of this disease.
Publication Title
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways.
Publication Title
High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina Genome Analyzer, Illumina Genome Analyzer II
Description
To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer. Overall design: Sequencing of approximately 18-35 nt small RNAs from paired samples of normal, tumor and tumor-adjacent tissue for five breast cancer patients
Publication Title
Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 320 Downloadable Samples
- NextSeq 500
Description
Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
Publication Title
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples