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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- 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
- 67 Downloadable Samples
Illumina HiSeq 2000
Description
Mutations in the mitochondrial DNA (mtDNA) have been proposed to be essential for metabolic adaptation, and because metabolism is intrinsically associated with multiple disease states, including obesity, we hypothesized that changes in the mtDNA would significantly influence adiposity and gene expression in response to diet. To test these predictions we used Mitochondrial-Nuclear eXchange mice, which have nuclear and mitochondrial genomes that have been exchanged from different M. musculus strains. Overall design: Purpose: Mutations in the mitochondrial DNA (mtDNA) have been proposed to be essential for metabolic adaptation, and because metabolism is intrinsically associated with multiple disease states, including obesity, we hypothesized that changes in the mtDNA would significantly influence adiposity and gene expression in response to diet. To test these predictions we used Mitochondrial-Nuclear eXchange mice, which have nuclear and mitochondrial genomes that have been exchanged from different M. musculus strains. Methods: Wild type (C57BL6/J – C57n:C57mt and C3H/HeN - C3Hn:C3Hmt) and MNX (C57n:C3Hmt and C3Hn:C57mt) mouse were weaned with Chor diet and continued with Chow or changed to high-fat diet from 6 to 12-13 weeks of age. RNA samples were isolated from white adipose tissues collected from epididymal (eWAT) and inguinal (iWAT) fat, representing visceral and subcutaneous fat depots, respectively with RNeasy kit (Qiagen). Reverse transcribed cDNA libraries were sequenced with an Illumina HiSeq 2000. Read mapping was conducted with a proprietary algorithm by Expression Analysis (www.q2labsolutions.com), and read counts were used as input for differential expression analysis in DESeq2 version 1.10.1, using default settings. Results: Using an optimized data analysis workflow, we mapped about 20 million sequence reads per sample to the mouse genome (build mm9). Transcriptional changes were interrogated for 961 genes previously reported to be associated with fat metabolism and 29,209 genes representing the entire mouse transcriptome. These results show that the C57 mtDNA increased the number of DE genes in response to high fat diet in mice harboring the C3H nuclear genome (209% increase; C3Hn:C57mt versus C3Hn:C3Hmt, 165/79) and the C3H mtDNA decreased response in animals carrying the C57 nucleus (46% decrease; C57n:C3Hmt versus C57n:C57mt, 112/206) in eWAT (Figure 2B). Similarly, the high fat diet resulted in 25 and 231 DE genes in the C3Hn:C3Hmt and C3Hn:C57mt iWAT, respectively, and 344 and 143 DE genes in C57n:C57mt and C57n:C3Hmt iWAT. This corresponded to a 924% increase in the number of DE genes responding to high fat diet C3Hn:C57mt versus C3Hn:C3Hmt, and a decreased response (58% decrease) in C57n:C3Hmt relative to C57n:C57mt iWAT. Further analysis showed that each MNX and corresponding wild-type shared and had distinct DE genes in eWAT and iWAT. Conclusions: Results also show that the degree of transcriptional response influenced by the mtDNA can vary based upon the type of adipose tissue, suggesting that mtDNA background can have varying effects on the number of nuclear genes differentially responding to stimuli, depending upon tissue and location.
Publication Title
Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions and its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalyzing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. Using a combination of literature information, transcription factor prediction models and genome-wide expression arrays, we inferred the regulatory network of IRG1 in mouse and human macrophages.
Publication Title
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Primary human hepatocytes (PHHs) are a liver-specific cell subtype, and we have shown that these cells respond in a unique manner to the introduction of hepatitis C viral RNA (HCV vRNA) derived from different genotypes of the virus.
Publication Title
Transmitted/founder hepatitis C viruses induce cell-type- and genotype-specific differences in innate signaling within the liver.
Sample Metadata Fields
Specimen part
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SRP071058- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
B cells provide humoral immunity by differentiating into antibody secreting plasma cells. Differentiation is dependent upon division and transcriptional changes, with commitment to B cell lineages associated with epigenetic changes. Analysis of early transcriptional and epigenetic events in B cell differentiation revealed that plasmablasts and plasma cells undergo dynamic changes in gene expression and a progressive DNA hypomethylation targeted to at least 10% of genes/loci. Of the differentially methylated loci, more than 99.7% were demethylated during differentiation and these clustered in cis-regulatory features such as enhancers and transcription factor binding sites. Changes in gene expression and DNA methylation coincided with each other at specific divisions during differentiation and inhibition of DNA methylation resulted in augmented plasma cell commitment in a division-dependent manner. These data identify a major epigenetic reprogramming event during early B cell differentiation coupled division and provide an approach to modulating humoral immune responses. Overall design: Splenic B cells (B220+ CD43-) from naïve C57/BL6J mice were labeled with CFSE or CTV and transferred into uMT mice and allowed to rest overnight prior to challenge with LPS. Three days post challenge adoptively transferred B cells representing distinct divisions were sorted out for molecular analysis. These divisions are labelled Div0, Div1, Div3, Div5, Div8- and Div8+. Division 8- refers to cells that divided at least 8 times but were CD138-, whereas Division 8+ refers to cells that divided at least 8 times but were CD138+. Cells were subjected to RNA-seq and Reduced Representation Bisulfite Sequencing.
Publication Title
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility).
Publication Title
Differential RNAs in the sperm cells of asthenozoospermic patients.
Sample Metadata Fields
No sample metadata fields
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