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GSE18791
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
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study, we examined differential gene expression in nave human CD4+ T cells, as well as in effector Th1, Th17-negative and Th17-enriched CD4- T cell subsets. We observed a marked enrichment for increased gene expression in effector CD4+ T cells compared to naive CD4+ among immune-mediated disease oci genes. Within effector T cells, expression of disease-associated genes was increased in Th17-enriched compared to Th17-negative cells.
Publication Title
Effector CD4+ T cell expression signatures and immune-mediated disease associated genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene segregates with most autoimmune diseases; its risk allele encodes overactive PTPN22 phosphatases that alter B cell receptor (BCR) signaling potentially involved in the regulation of central B cell tolerance. To assess whether PTPN22 risk allele affects the removal of developing autoreactive B cells, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from asymptomatic healthy individuals carrying one or two PTPN22 risk allele(s). We found that new emigrant/transitional and mature naive B cells from PTPN22 risk allele carriers contained high frequencies of autoreactive clones compared to non-carrier control donors. Hence, a single PTPN22 risk allele has a dominant effect on altering autoreactive B cell counterselection, suggesting that early B cell tolerance checkpoint defects precede the onset of autoimmunity. In addition, gene array experiments comparing mature nave B cells from healthy individuals carrying or not PTPN22 risk allele(s) revealed that the strength of association of PTPN22 for autoimmunity, second in importance only to the MHC, may not only be due to BCR signaling alteration but also to the regulation of other genes, which themselves have also been identified as involved in the development of autoimmune diseases.
Publication Title
The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 13 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Placentation of the conceptus to the surface epithelium is governed through a tightly regulated temporal and spatial window. Premature exogenous steriod exposure causes a shift in the maternal tissue's receptivity and prevents proper placentation.
Publication Title
Effects of aberrant estrogen on the endometrial transcriptional profile in pigs.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Basilar papillae (i.e.auditory epithelia) were isolated from 4-day-old chickens and sectioned into low, middle, and high frequency segments. RNA was isolated from each segment separately, amplified using a two-cycle approach, biotinylated, and hybridized to Affymetrix chicken whole-genome arrays.
Publication Title
Gene expression gradients along the tonotopic axis of the chicken auditory epithelium.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
We compared transcriptomic profiles of hepatic macrophages between sham operated rats, rats 3 days and 10 days after partial portal vein ligation (PPVL) surgery (n=3). The number of genes with a significant change was most numerous in Sham vs 3 days, followed by Sham vs 10 days and 3 days vs 10 days.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aberrations in epigenetic processes, such as histone methylation, can lead to cancer. Retinoblastoma Binding Protein 2 (RBP2)(also called JARID1A or KDM5A) can demethylate tri- and di-methylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the MEN1 tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by pRB. Here we show RBP2 loss promotes cellular differentiation in vitro. We use mouse expression array 430 2.0 array to profile gene expression patterns of Rbp2f/f and Rbp2-/- ES cells in ES cell medium and after 6 days in ES cell medium without LIF.
Publication Title
Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. To define mechanisms that might be contributing to the differential IL-23-induced STAT3 activation between individuals, we examined mRNA expression differences in CD8+CD45RO+ memory T cells between IL-23 responsive and non-responsive individuals.
Publication Title
Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Peripheral tolerance induction is critical for the maintenance of self-tolerance and can be mediated by immunoregulatory T cells or by direct induction of T cell anergy or deletion. While the molecular processes underlying anergy have been extensively studied, little is known about the molecular basis for peripheral T cell deletion. Here, we determined the gene expression signature of peripheral CD8+ T cells undergoing deletional tolerance, relative to those undergoing immunogenic priming or lymphopenia-induced proliferation. From these data, we report the first detailed molecular signature of cells undergoing deletion.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The roles of histone demethylase RBP2 in gene expression were assessed using gene expression profiling experiments with wild type and RBP2-/- primary MEFs. Several cytokine genes including SDF1 and Kit ligand were upregulated upon inactivation of RBP2.
Publication Title
The retinoblastoma binding protein RBP2 is an H3K4 demethylase.
Sample Metadata Fields
No sample metadata fields
View Samples