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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- Homo sapiens
- 101 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Analysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Analysis of cryopreservation effects on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with a strong loss of signal intensities to background levels for several transcripts.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Analysis of long-term freezing on the stability of transcriptome profiles in PAXgene stabilized whole blood samples. In the present study it was tested if long-term freezing of PAXgene RNA tubes (up to one year) has an influence on the transcriptome profile of peripheral whole blood samples. Results indicated that gene expression profiles of whole blood samples stabilized with PAXgene RNA tubes remain stable for at least 1 year.
Publication Title
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples
GSE84051- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule VLX600.
Publication Title
Iron chelators target both proliferating and quiescent cancer cells.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples GSE53631- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray based mRNA profiling was used to charactarize and compare the gene expression in cells grown as monolayer or spheroids.
Publication Title
Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out.
Publication Title
Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.
Sample Metadata Fields
Cell line, Treatment
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of polysaccharides, proteins, and extracelluar (e)DNA, with eDNA being required for the formation and integrity of biofilms. Here we demonstrate that the spatial and temporal release of eDNA is regulated by BfmR, a regulator essential for Pseudomonas aeruginosa biofilm development. The expression of bfmR coincided with localized cell death and DNA release, with high eDNA concentrations localized to the outer part of microcolonies in the form of a ring and as a cap on small clusters. Additionally, eDNA release and cell lysis increased significantly following bfmR inactivation. Genome-wide transcriptional profiling indicated that bfmR was required for repression of genes associated with bacteriophage assembly and bacteriophage-mediated lysis. In order to determine which of these genes were directly regulated by BfmR, we utilized chromatin immunoprecipitation (ChIP) analysis to identify the promoter of PA0691, termed here phdA, encoding a previously undescribed homologue of the prevent-host-death (Phd) family of proteins. Lack of phdA expression coincided with impaired biofilm development, increased cell death and bacteriophage release, a phenotype comparable to bfmR. Expression of phdA in bfmR biofilms restored eDNA release, cell lysis, release of bacteriophages, and biofilm formation to wild type levels. Moreover, overexpression of phdA rendered P. aeruginosa resistant to lysis mediated by superinfective bacteriophage Pf4 which was only detected in biofilms. The expression of bfmR was stimulated by conditions resulting in membrane perturbation and cell lysis. Thus, we propose that BfmR regulates biofilm development by controlling bacteriophage-mediated lysis and thus, cell death and eDNA release, via PhdA.
Publication Title
The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA release during biofilm development through PhdA.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
A hallmark of the biofilm architecture is the presence of microcolonies. However, little is known about the underlying mechanisms governing microcolony formation. In the human pathogen Pseudomonas aeruginosa, microcolony formation is dependent on the two-component regulator MifR, with mifR mutant biofilms exhibiting an overall thin structure lacking microcolonies, and overexpression of mifR resulting in hyper-microcolony formation. Here, we made use of the distinct MifR-dependent phenotypes to elucidate mechanisms associated with microcolony formation. Using global transcriptomic and proteomic approaches, we demonstrate that cells located within microcolonies experience stressful, oxygen limited, and energy starving conditions, as indicated by the activation of stress response mechanisms and anaerobic and fermentative processes, in particular pyruvate fermentation. Inactivation of genes involved in pyruvate utilization including uspK, acnA and ldhA abrogated microcolony formation in a manner similar to mifR inactivation. Moreover, depletion of pyruvate from the growth medium impaired biofilm and microcolony formation, while addition of pyruvate significantly increased microcolony formation. Addition of pyruvate partly restored microcolony formation in mifR biofilms. Moreover, addition of pyruvate to or expression of mifR in lactate dehydrogenase (ldhA) mutant biofilms did not restore microcolony formation. Consistent with the finding of denitrification genes not demonstrating distinct expression patterns in biofilms forming or lacking microcolonies, addition of nitrate did not alter microcolony formation. Our findings indicate the fermentative utilization of pyruvate to be a microcolony-specific adaptation to the oxygen limitation and energy starvation of the P. aeruginosa biofilm environment.
Publication Title
Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation.
Sample Metadata Fields
No sample metadata fields
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