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GSE11292
Homo sapiens
77 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human FOXP3+CD25+CD4+ regulatory T cells (Tregs) play a dominant role in the maintenance of immune homeostasis. Several genes are known to be important for murine Tregs, but for human Tregs the genes and underlying molecular networks controlling the suppressor function still largely remain unclear. We here performed a high-time-resolution dynamic analysis of the transcriptome during the very early phase of human Treg/ CD4+ T-effector cell activation. After constructing a correlation network specific for Tregs based on these dynamic data, we described a strategy to identify key genes by directly analyzing the constructed undirected correlation network. Six out of the top 10 ranked key hubs are known to be important for Treg function or involved in autoimmune diseases. Surprisingly, PLAU (the plasminogen activator urokinase) was among the 4 new key hubs. We here show that PLAU was critical for expression regulation of FOXP3, EOS and several other important Treg genes and the suppressor function of human Tregs. Moreover, we found Plau inhibits murine Treg development and but promotes the suppressive function. Further analysis unveils that PLAU is particularly important for memory Tregs and that PLAU mediates Treg suppressor function via STAT5 and ERK signaling pathways. Our study shows the potential for identifying novel key genes for complex dynamic biological processes using a network strategy based on high-time-resolution data, and highlights a critical role of PLAU in both human and murine Tregs. The construction of a dynamic correlation network of human Tregs provides a useful resource for the understanding of Treg function and human autoimmune diseases.
Publication Title
PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3
Publication Title
1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The concept of immune regulation/suppression has been well-established. With thymus-derived CD4 CD25 regulatory T (TR) cells, it became clear that a variety of additional peripherally induced TR cells play vital roles in protection from many harmful immune responses including intestinal inflammation. In the present study, we have analyzed in vivo-induced Ag-specific CD4 TR cells with respect to their molecular and functional phenotype. By comparative genomics we could show that these Ag-specific TR cells induced by chronic Ag stimulation in vivo clearly differ in their genetic program from naturally occurring thymus-derived CD4 CD25 TR cells. This distinct population of induced TR cells express neither CD25 nor the TR-associated transcription factor Foxp3. Strikingly, CD25 is not even up-regulated upon stimulation. Despite the lack in Foxp3 expression, these in vivo-induced CD25 TR cells are able to interfere with an Ag-specific CD8 T cell-mediated intestinal inflammation without significant increase in CD25 and Foxp3 expression. Thus, our results demonstrate that in vivo-induced Ag-specific TR cells represent a distinct population of Foxp3 CD25 TR cells with regulatory capacity both in vitro and in vivo.
Publication Title
Chronic antigen stimulation in vivo induces a distinct population of antigen-specific Foxp3 CD25 regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Expression analysis revealed that UBD is a down-stream element of Foxp3 in human activated regulatory CD4+ T cells (Treg).
Publication Title
UBD, a downstream element of FOXP3, allows the identification of LGALS3, a new marker of human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Goals and objectives of this study: to identify genes preferentially induced in human CD4+CD25hi Treg cells following T-cell activation with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goals and objectives of this study: to identify genes of the Treg signature induced by consitutive expression of GARP or FOXP3 in antigen-specific Th cells with potential role for stabililization & maintenance of the regulatory program.
Publication Title
GARP: a key receptor controlling FOXP3 in human regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Comparison of Arabidopsis mutants lacking CAF-1 subunits
Publication Title
Functional genomic analysis of CAF-1 mutants in Arabidopsis thaliana.
Sample Metadata Fields
Age, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Dengue virus (DENV) infection is one of the most serious public health problems worldwide. A recent dengue outbreak in Paraguay (2007-2009) presented unusual manifestations such as hepatitis, encephalitis, pulmonary as well as cardiac disorders associated with 50% of deaths caused by dengue in the country. Despite the knowledge on inflammatory responses observed during the course of disease, the role of innate immune cells in the control of virus replication influencing clinical outcome is poorly defined. Using two clinical isolates of the virus, a non-fatal case of classical DF (DENV3/290) and a fatal case of DF with visceral complications (DENV3/5532), we sought to determine the profile of dengue infection in human dendritic cell, a major innate immune cell population. Compared to classical DENV3/290, the strain DENV3/5532 displayed higher replicative ability in mdDCs. In addition, DENV3/5532 was found to induce elevated production of pro-inflammatory cytokines associated with higher rates of programmed cell death. The observed phenotype was due to viral replication in mdDCs and TNF appeared to display a protective effect on virus-induced mdDCs apoptosis. These results suggest that the fatal case DENV3/5532 isolate modulates dendritic cell survival as well as inflammatory mediators synthesis.
Publication Title
Dengue virus type 3 isolated from a fatal case with visceral complications induces enhanced proinflammatory responses and apoptosis of human dendritic cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 303 Downloadable Samples
IlluminaHiSeq2500
Description
Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials, and offer a cost effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically-defined poly(ethylene glycol) (PEG) hydrogels and cultured in serum-free media to model cellular interactions of the developing brain. The precursors self-assembled into 3-dimensional (3D) neural constructs with cortically organized neuronal and glial cells, interconnected vascular networks, and ramified microglia. Replicate constructs were highly reproducible by RNA sequencing (Spearman's correlation coefficients, ? = 0.97) and robustly expressed neurogenesis, vasculature development, and microglia genes. Finally, linear support vector machines were used to construct a predictive model from RNA sequencing data for 240 neural constructs treated with 60 toxic and non-toxic chemicals, which then correctly classified 9/10 blinded compounds. Overall design: Note that all cell types were derived from the H1 human embryonic stem cell line. 11 samples for initial quality control (triplicate day 13 neural progenitor cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells; quadruplicate day 21 neural progenitor cells cocultured with mesenchymal stem cells and endothelial cells and migroglia/macrophage precursor cells), quadruplicate samples of H1 ES cells as a control for comparing to untreated toxicity study samples, and 288 samples associated with toxicity screening (all samples formed using neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors).
Publication Title
Uniform neural tissue models produced on synthetic hydrogels using standard culture techniques.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to investigate the transcriptomes of cSCC and actinic keratoses (AK), to elucidate key differences between precursor AK lesions and invasive carcinoma.
Publication Title
Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples