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GSE10584
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to elucidate the molecular mechanism giving rise to the rare In(Lu) type of Lu(a-b-) blood group phenotype we compared the transcriptome of normal and In(Lu) erythroblasts at different stages of maturation. Many erythroid-specific genes had reduced transcript levels suggesting the phenotype resulted from a transcription factor abnormality. A search for mutations in erythroid transcription factors revealed mutations in the promoter or coding sequence of EKLF in 21 of 24 individuals with the In(Lu) phenotype. In all cases the mutant EKLF allele occurred in the presence of a normal EKLF allele. Individuals with the In(Lu) phenotype have no reported pathology indicating that one functional EKLF allele is sufficient to sustain human erythropoiesis. These data provide the first description of inactivating mutations in human EKLF and the first demonstration of a blood group phenotype resulting from mutations in a transcription factor.
Publication Title
Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conjunctival samples from 60 individuals with and without the clinical signs of active trachoma were analysed on the U133 Plus 2.0 arrays. Global transcriptional changes characteristic of disease and infection phenotypes were identified. Two analysis methods found large numbers of differentially regulated genes and the existence of networks of co-expressed genes. There were signatures characteristic of the host defence response with evidence supporting infiltration of various types of leukocytes and activation of innate responses of epithelial cells. Two separate methods could classify disease and infection phenotype based on transcription signatures with 70% accuracy. These results provide an insight into the complexity of the acute response in trachoma but are able to partly explain the biology of trachoma through the identification of pathways and gene expression sets useful to future studies on chlamydial immunopathogenesis.
Publication Title
Human conjunctival transcriptome analysis reveals the prominence of innate defense in Chlamydia trachomatis infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Race
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
NextSeq 500
Description
We profiled how animals RNA expression changes in response to osmotic stress, how lin-45 mutants have an altered response to osmotic stress, and how maternal preconditioning at 300 mM NaCl modifies progeny response to 500 mM NaCl Overall design: Examination of total RNAseq at 50 mM NaCl, 500 mM NaCl, and 500 mM NaCl from maternally preconditioned animals
Publication Title
Insulin-like signalling to the maternal germline controls progeny response to osmotic stress.
Sample Metadata Fields
Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this cardiac aging model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function.
Publication Title
Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Peptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
Publication Title
Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD20 is a clinically validated target for Non-Hodgkins lymphomas and autoimmune diseases. Interactions of CD20 with the B cell receptor (BCR) and components of the BCR signaling cascade have been reported. In this study we show that antibodies against CD20 or activation of the BCR by specific antibodies induce very similar expression patterns of up- or down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa.
Publication Title
Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have generated tumorigenic (S2N) and non-tumorigenic (S2), normal-like to basal-like breast cancer cell lines from primary tumors. At high in vivo inoculation cell numbers of 10^6 cells/mouse both S2N and S2 monolayer as well as sphere culture cells grew at similar rates. However, at low inoculation cell numbers down to 10^3 cells only S2N sphere cells generated xenograft tumors. mRNA profiling revealed a unique cluster pattern of the tumorigenic S2N sphere cells, but a detailed analysis of TIC relevant transcription factors like Oct3, Sox and Nanog family members, Myc, Slug or Twist1 revealed no consistently increased expression in the highly tumorigenic cell lines. Our data indicate that the intrinsic genetic and functional markers investigated are not solely indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells.
Publication Title
Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response.
Publication Title
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. A Nugent scoring system serves as a proxy for determining the ratio of lactobacilli to other vaginal inhabitants where a high score usually represents a diseased state, whilst an intermediate score represents a warning zone. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate score, the effect of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 on the microbiota and host response. The probiotic treatment did not result in changes to clinical parameters such as dryness, irritation and comfort, compared to when placebo was applied. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the proportional abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response and multiplex cytokine analysis showed up-regulation of IL-5. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle trigger molecular changes induced by the host to instillation of probiotic strains.
Publication Title
A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
As part of a larger study on Cell-specific vacuolar calcium compartmentation regulates apoplastic calcium concentration, gas exchange and plant productivity we compared the transcriptome of 40day old CAX1/CAX3 double mutants to Col-0 wildtype plants.
Publication Title
Cell-specific vacuolar calcium storage mediated by CAX1 regulates apoplastic calcium concentration, gas exchange, and plant productivity in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples