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GSE31264
Homo sapiens
17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders.
Publication Title
HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders.
Publication Title
HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The complete specrtum of genes that are subject to regulation by Hnf1b in mouse kidney cells is not known.
Publication Title
Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD27 and CD45RA can be used to split T cells into 4 subsets, nave cells, CD27+CD45RA+, central memory cells CD27+CD45RA-, effector memory cells CD27-CD45RA-, effector memory CD45RA re-expressing cell, CD27-CD45RA+. It is with in this final EMRA subset that it is belived the senenscent T cells reside. Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP), to date a SASP has not been demonstrated in T cells.
Publication Title
Human CD8<sup>+</sup> EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors.
Publication Title
Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Methods: 70 treatment-nave patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.50.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy.
Publication Title
Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Publication Title
Genomic analysis of reactive astrogliosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
NextSeq 500
Description
We have previously demonstrated older skin exhibits increased sterile inflammation 6 hours after saline-injection. In this work, we examined whether p38MAPK inhibitor in vivo would attenuate this non-specific inflammatory response towards saline in elder individuals (=65 years). Overall design: Skin mRNA profiles 6 hours after saline injection were studied before and after losmapimod treatment.
Publication Title
Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome profiles derived from the site of human disease has led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene co-expression modules by cell type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach towards identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.
Publication Title
Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice.
Publication Title
Shifts in the vascular endothelial growth factor isoforms result in transcriptome changes correlated with early neural stem cell proliferation and differentiation in mouse forebrain.
Sample Metadata Fields
Specimen part
View Samples