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SRP109674
Mus musculus
43 Downloadable Samples
Illumina HiSeq 2500
Description
Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. Overall design: For bleomycin experiments, 8 week old C57Bl/6 female mice were used.The bleomycin model was established with daily subcutaneous injections of bleomycin (100uL at 1U/mL) into the back skin. Experimental timepoints include: saline, 2 weeks bleo, 4 weeks bleo, 6 weeks recovery, and 10 weeks recovery.
Publication Title
Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To obtain a genomic view of hepatocyte nuclear factor-4 (HNF-4) in the regulation of the inflammatory response, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokines in a model of knock-down HNF-4 HepG2 cells. The results indicate an extensive role for HNF-4 plays in the regulation of a large number of the liver-specific genes. Majority of genes (71%) affected by cytokine treatment are also affected by HNF-4 knock-down. This significant overlap suggests that HNF-4 may play a role in regulating the cytokine-induced inflammatory response.
Publication Title
Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).
Publication Title
Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
To provide a comprehensive understanding of how GC affect adipose tissue and adipocyte function, we analyzed patterns of gene expression after culture of abdominal subcutaneous (sc) and omental (Om))
Publication Title
Pathways regulated by glucocorticoids in omental and subcutaneous human adipose tissues: a microarray study.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Atopic dermatitis and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. We show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of atopic dermatitis-specific Th2 and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in atopic dermatitis, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naïve mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in atopic dermatitis and psoriasis. Overall design: Eight- to 12-week old male mice were used. TWEAK-deficient animals were bred in house on the C57BL/6 background, and Fn14-deficient animals on a BALB/c. Atopic Dermatitis-like disease was induced by epicutaneous treatment with HDM extract (10 µg/mouse and treatment) and SEB (500 ng/mouse and treatment) given in 2 cycles on days 1 and 4, and 14 and 17, on the shaved and tape-stripped back skin over a 23 day period.
Publication Title
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis.
Sample Metadata Fields
Treatment, Subject
View Samples- Arabidopsis thaliana
- 27 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Ozone pollution decreases plant growth and yield worldwide. Some of the effects are genetically-mediated and are reported to involve G-protein signaling pathways. Effects of ozone on gene expression were examined in wild-type and G-protein null mutants to determine affected genes and to determine differential responses that may help define affected pathways.
Publication Title
Minimal influence of G-protein null mutations on ozone-induced changes in gene expression, foliar injury, gas exchange and peroxidase activity in Arabidopsis thaliana L.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we demonstrate the variation of host gene expression which underlies the contrasting hepatic pathology observed between two inbred mouse strains following schistosome infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in BALB/c and CBA mice during an active Schistosoma japonicum infection. Here, we show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. Generally, up-regulated genes were largely associated with immune and inflammatory responses, antigen processing and cytokine/chemokine activity. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with significantly greater accumulation of neutrophils at granulomatous regions, compared to CBA mice. In contrast, up-regulated expression of eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the greater degree of liver damage in these mice. Genes involved in fibrosis showed similar levels of expression in both mouse strains. Genes associated with Th1 and Th2 responses showed no significant differences in expression between strains. These results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. Furthermore, this improved understanding of schistosome immunopathogenesis in the murine model will provide the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.
Publication Title
Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus, Schistosoma japonicum
- 8 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs) and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1), members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12) and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14) and markers of alternatively-activated macrophages (e.g. Retnla) during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic zone of granulomas. Furthermore, striking up-regulation of neutrophil markers and the localisation of neutrophils and the neutrophil chemokine S100A8 to fibrotic areas suggests the involvement of neutrophils in S. japonicum-induced hepatic fibrosis. These results further our understanding of the immunopathogenic and, especially, chemokine signalling pathways that regulate the development of S. japonicum-induced granulomas and fibrosis and may provide correlative insight into the pathogenesis of other chronic inflammatory diseases of the liver where fibrosis is a common feature.
Publication Title
Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of RNAs extracted from early passage and late passage (immortalized) mouse embryonic fibroblasts (MEFs)
Publication Title
A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Migrating schistosomula are an important stage of the schistosome lifecycle and represent a key target for elimination of infection by natural and vaccine induced host immune responses. To gain a better understanding of how these parasites initiate a primary host immune response we have characterised the host lung response to migrating Schistosoma japonicum schistosomula using a combination of histochemistry, microarrays and quantitative cytokine analysis. Our data suggest that, during a S. japonicum infection, actively migrating schistosomula induce a Type-2 cytokine response in the lung that may support the subsequent development of a CD4+ T helper 2 (Th2) response against egg antigens. This hypothesis is supported by the fact that schistosomula and schistosome eggs are known to express important Th2-inducing antigens such as omega-1, peroxiredoxin, kappa-5 and IPSE/alpha1. The host lung response to migrating schistosomula was associated with increased numbers of macrophages and expression of markers for alternatively activated macrophages (AAM) in the lung. Activation of AAM in the lung and at the systemic level could lead to the modulation of the host immune response to favour parasite survival. Induction of these cells could also contribute to diminished inflammatory responses to, for example, allergy and asthma that are known to be associated with helminth infections. These data enhance our understanding of the mechanisms whereby schistosomes may evade the immune response and the mechanisms by which schistosome infection can help influence the host response following exposure to allergenic stimuli.
Publication Title
Migrating Schistosoma japonicum schistosomula induce an innate immune response and wound healing in the murine lung.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples