Hodgkin's lymphoma (HL) is one of the most frequent hematological malignancies. Due to its extraordinary composition, few tumor cells surrounded by a reactive infiltrate, HL can be seen as an ideal model system for research focusing on tumor immunology. In fact, the tumor cells of HL, so called Hodgkin/Reed-Sternberg (HRS) cells attract CD4+ T cells, which then build rosettes with the HRS cells. HRS cells further modulate the tumor microenvironment with the help of CD4+ T cells to avoid tumor rejection. Here, we mimicked this scenario using compatible CD4+ T cells receiveing data of profound interactions for the first time, as former studies were performed with allogeneic donors. Finally, we genetically retargeted compatible CD4+ T cells to kill HRS cells.
Tumor-infiltrating HLA-matched CD4(+) T cells retargeted against Hodgkin and Reed-Sternberg cells.
Cell line
View SamplesAnalysis of HEK293T cells overexpressing ZAPS (zinc finger antiviral protein, short form; NP_078901), which is a member of the PARP (poly (ADP-ribose) polymerase)-superfamily. Results of gene profiles provide insight into the role of ZAPS in innate immunity.
ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses.
Specimen part, Cell line
View SamplesAmong colicin producing E. coli, colicin M producing strains are the most frequently present in natural populations. Bacteria must be able to sense and respond to unfavourable conditions, resulting in adaptive responses. To gain insight into colicin M ecological role and the purposes related to antimicrobial therapy, the effects of subinhibitory concentrations of colicin M on E. coli whole genome transcription was investigated. We used microarray analysis to follow differential gene expression in E. coli upon colicin M exposure. Colicin M inhibits peptidoglycan synthesis altering expression of genes involved in envelope stress, osmotic and other stresses, exopolysaccharide prodoction, biofilm formation, and cell motility.
Global transcriptional responses to the bacteriocin colicin M in Escherichia coli.
Treatment
View SamplesXBP1 is a transcription factor that is induced by unconventional splicing associated with endoplasmic reticulum stress and plays a role in development of liver and plasma cells. We previously reported that brain derived neurotrophic factor (BDNF) leads to splicing of XBP1 mRNA in neurites, and that XBP1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how XBP1 plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but this induction was reduced in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated induction of Npy and Calb1 was confirmed by quantitative RT-PCR. In neurons lacking in Xbp1, upregulation of GABAergic markers was attenuated. Impaired BDNF-induced neurite extension in Xbp1 knockout neurons might be mediated by disturbed BDNF-induced differentiation of GABAergic interneurons.
Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1.
Specimen part
View SamplesType 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo. Overall design: There are three experiments in this submission. All are in human islets or islet cell types. The first is a comparison of miRNA levels in sorted alpha versus beta cells. There is one replicate for this experiment. The second experiment is to measure the expression of miRNAs in whole islets as a function of glucose levels. There are three levels and one replicate for each condition. The third exeriment is a comparison of whole islets taken from human donors that were suspected/confirmed Type 2 diabetic or considered controls. There are 3 controls and 4 T2D samples.
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
No sample metadata fields
View SamplesType 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing ß-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human ß-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased ß-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM. Overall design: Identification of miRNA-target interaction in human islets using HITS-CLIP, one mRNA library and one miRNA library
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
No sample metadata fields
View SamplesTo investigate effects of intake of mulberry leaves on hyperlipidemia, we performed gene expression profiling on rat liver by microarray analysis.
Ameliorative effects of mulberry (Morus alba L.) leaves on hyperlipidemia in rats fed a high-fat diet: induction of fatty acid oxidation, inhibition of lipogenesis, and suppression of oxidative stress.
No sample metadata fields
View SamplesThe prognosis of the patients with neuroblastoma largely depends on the biological characterisitics. Neuroblastoma tissues obtained before any treatments were analyzed for gene expression using Affymetrix array.
A robust method for estimating gene expression states using Affymetrix microarray probe level data.
Specimen part
View SamplesTo uncover molecular mechanisms underlying reduction of responses to restraint stress by racemic (R,S)-linalool inhalation, gene expression profiling at the hypothalamus of restraint stressed rats exposed to racemic (R,S)-linalool was carried out.
Inhalation of a racemic mixture (R,S)-linalool by rats experiencing restraint stress alters neuropeptide and MHC class I gene expression in the hypothalamus.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells.
Sex, Age, Specimen part, Treatment
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