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GSE25713
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
- 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- Drosophila melanogaster
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Crystal cells are one of the 3 Drosophila blood cell lineages and represent less than 5% of the total hemocytes in wild type larvae. There development is notably controlled by mlf (myeloid leukemia factor), which regulate their number by stabilising the lineage-specific transcription factor Lozenge. To gain insight into the biology of this blood cell lineage and its regulation by mlf, we established the gene expression profile of the circulating crystal cells in wildtype and mlf mutant third instar larvae. This study provides a rich source of information to further characterise crystal cell function and regulation. In addition our data show that mlf is a major regulator of crystal cell gene expression programm and that mlf mutation leads to the accumulation of misdifferentiated crystal cells. Overall design: RNA expression profiles of sorted lz-GAL4,UAS-GFP+ circulating blood cells from wild type and mlf-/- third instar Drosophila larvae were generated by deep sequencing, in triplicate, using Illumina HiSeq2500 sequencing platform.
Publication Title
Control of RUNX-induced repression of Notch signaling by MLF and its partner DnaJ-1 during Drosophila hematopoiesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage <i>in vitro</i>.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Here, we report the generation of human induced Pluripotent Stem (iPS) cell reporter line in which a venus fluorescent protein have been introduced into the PAX7 locus. We use microarrays to compare the transcriptome of PAX7-venus+ cells after 3 weeks of myogenic differentiation to that of undifferentiated iPS
Publication Title
Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage <i>in vitro</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Here, we report the generation of human induced Pluripotent Stem (iPS) cell reporter line in which a venus fluorescent protein have been introduced into the MYOGENIN (MYOG) locus. We use microarrays to compare the transcriptome of MYOG-venus+ cells after 3 weeks of myogenic differentiation to that of undifferentiated iPS
Publication Title
Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage <i>in vitro</i>.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Here, we use microarrays to compare the transcriptome of mouse Pax7-GFP ES reporter cell line after 3 weeks of myogenic differentiation in vitro to that of undifferentiated ES
Publication Title
Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage <i>in vitro</i>.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Posterior embryonic axis develops from neuromesodermal progenitors which differentiate into neural tube and paraxial mesoderm
Publication Title
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell-derived tissues have wide potential for modelling developmental and pathological processes as well as cell-based therapy. However, it has proven difficult to generate several key cell types in vitro, including skeletal muscle. In vertebrates, skeletal muscles derive during embryogenesis from the presomitic mesoderm (PSM). Using PSM development as a guide, we establish conditions for the differentiation of monolayer cultures of human pluripotent stem (hPSC) cells into PSM-like cells without the introduction of transgenes or cell sorting. We differentiated human PSCs in serum-free medium supplemented with Chir99021 only (C medium) or with also the Bmp inhibitor LDN193189 (CL medium). In vivo, the PSM cells are first expressing MSGN1 (posterior PSM marker) and then mature to express Pax3 (anterior PSM marker). After 4-5 days of differentiation of hPSCs, MSGN1-positive cells were FACS-sorted and their transcriptome analyzed.
Publication Title
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Sample Metadata Fields
Treatment
View Samples