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GSE52081
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The physiological function of the immune system and the response to therapeutic immunomodulators may be sensitive to combinatorial cytokine micro-environments that shape the responses of specific immune cells. Previous work shows that paracrine cytokines released by virus-infected human dendritic cells (DC) can dictate the maturation state of nave DCs. To understand the effects of paracrine signaling, we systematically studied the effects of combinations cytokines in this complex mixture in generating an antiviral state. After nave DCs were exposed to either IFN or to paracrine signaling released by DCs infected by Newcastle Disease Virus (NDV), microarray analysis revealed a large number of genes that were differently regulated by the DC-secreted paracrine signaling. In order to identify the cytokine mechanisms involved, we identified 20 cytokines secreted by NDV infected DCs for which the corresponding receptor gene is expressed in nave DCs. By exposing cells to all combinations of 19 cytokines (leave-one-out studies) we identified 5 cytokines (IFN, TNF, IL-1, TNFSF15 and IL28) as candidates for regulating DC maturation markers. Subsequent experiments identified IFN, TNF and IL1 as the major synergistic contributors to this antiviral state. This finding was supported by infection studies in vitro, by T cell activation studies and by in vivo infection studies in mouse. Combination of cytokines can cause response states in DCs that differ from those achieved by the individual cytokines alone. These results suggest that the cytokine microenvironment may act via a combinatorial code to direct the response state of specific immune cells. Further elucidation of this code may provide insight into responses to infection and neoplasia as well as guide the development of combinatorial cytokine immunomodulation for infectious, autoimmune and immunosurveillance-related diseases.
Publication Title
Combinatorial cytokine code generates anti-viral state in dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray to characterize interferon stimulated genes in dendritic cells
Publication Title
Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Identifying the early gene program induced by GnRH would help understand how GnRH-activated signaling pathways modulate gonadotrope secretory response. We previously analyzed GnRH-induced early genes in LbT2 cells, however these lack GnRH self-potentiation, a physiological attribute of gonadotropes. To minimize cellular heterogeneity, rat primary pituitary cultures were enriched for gonadotropes by 40-60% using a sedimentation gradient. Given the limited number of gonadotropes, RNA was amplified prior to microarray analysis. Thirty-three genes were up-regulated 40 minutes after GnRH stimulation. Real-time PCR confirmed regulation of several transcripts including fosB, c-fos, egr-2 and rap1b, a small GTPase and member of the Ras family. GnRH stimulated rap1b gene expression in gonadotropes, measured by a sensitive single cell assay. Immunocytochemistry revealed increased Rap1 protein in GnRH-stimulated gonadotropes. These data establish rap1b as a novel gene rapidly induced by GnRH and a candidate to modulate gonadotropin secretion in rat gonadotropes.
Publication Title
Optimized amplification and single-cell analysis identify GnRH-mediated activation of Rap1b in primary rat gonadotropes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The dendritic cell (DC) is a master regulator of immune responses. Pathogenic viruses subvert normal immune function in DCs through the expression of immune antagonists. Understanding how these antagonists interact with the host immune system requires knowledge of the underlying genetic regulatory network that operates during an uninhibited antiviral response. In order to isolate and identify this network, we studied DCs infected with Newcastle Disease Virus (NDV), which is able to stimulate innate immunity and DC maturation through activation of RIG-I signaling, but lacks the ability to evade the human interferon response. To analyze this experimental model, we developed a new approach integrating genome-wide expression kinetics and time-dependent promoter analysis. We found that the genetic program underlying the antiviral cell state transition during the first 18-hours post-infection could be explained by a single regulatory network. Gene expression changes were driven by a step-wise multi-factor cascading control mechanism, where the specific transcription factors controlling expression changed over time. Within this network, most individual genes are regulated by multiple factors, indicating robustness against virus-encoded immune evasion genes. In addition to effectively recapitulating current biological knowledge, we predicted, and validated experimentally, antiviral roles for several novel transcription factors. More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell state transitions.
Publication Title
Antiviral response dictated by choreographed cascade of transcription factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We compared gene expression profiles of ALS patients with normal patients and with multifocal motor neuropathy (MMN) patients.
Publication Title
Differential gene expression in patients with amyotrophic lateral sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 150 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 120 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The aim of this data set is to measure the effect of rofecoxib and celecoxib on the transcription profile in an in vitro inflammation model. Transcription profiling was carried out using Affymetrix HG U-133A v2 microarrays.
Publication Title
Understanding multicellular function and disease with human tissue-specific networks.
Sample Metadata Fields
Sex, Specimen part, Race, Time
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure.
Publication Title
Neurobehavioral and transcriptional effects of acrylamide in juvenile rats.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples