Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared to other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We measured gene expression (Human Gene 1.0 ST Array, Affymetrix) in two series of experiments involving cells that were either susceptible or not susceptible to RV-C infection. In one experimental series, susceptible cells included whole sinus mucosal tissue specimens (n = 5), epithelial cell suspension from sinus tissue, and nasal epithelium obtained via brushing, while non-susceptible cells included monolayers of primary undifferentiated epithelial cells and transformed cell lines (n = 5). In a second experimental series, we compared three pairs of undifferentiated and fully differentiated (ALI) sinus epithelial cell cultures. We identified a total of 12 genes upregulated in RV-C susceptible cells (represented by 14 probe sets) encoding proteins localized to plasma membrane, and/or with predicted or functionally demonstrated receptor activity, including members of the Human MHC class II, stomatin, guanine nucleotide-binding, type I cytokine and atypical chemokine receptor and cadherin protein families.
Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.
Specimen part, Cell line, Subject
View SamplesUnderstanding the mechanism of SRC-1 dependent and independent E2 signaling in bone will provide a better understanding of the biology underlying osteoporosis.
Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen.
Specimen part, Cell line, Treatment
View SamplesTranscriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding for hundreds of TFs genome-wide. Here, we propose methods for TRN inference in a mammalian setting, using ATAC-seq data to influence gene expression modeling. We rigorously test our methods in the context of T Helper Cell Type 17 (Th17) differentiation, generating new ATAC-seq data to complement existing Th17 genomic resources (plentiful gene expression data, TF knock-outs and ChIP-seq experiments). In this resource-rich mammalian setting our extensive benchmarking provides quantitative, genome-scale evaluation of TRN inference combining ATAC-seq and RNA-seq data. We refine and extend our previous Th17 TRN, using our new TRN inference methods to integrate all Th17 data (gene expression, ATAC-seq, TF KO, ChIP-seq). We highlight new roles for individual TFs and groups of TFs (“TF-TF modules”) in Th17 gene regulation. Given the popularity of ATAC-seq (a widely adapted protocol with high resolution and low sample input requirements), we anticipate that application of our methods will improve TRN inference in new mammalian systems and be of particular use for rare, uncharacterized cell types. Overall design: Gene expression (RNA-seq) of naive and Th17- and Th0-polarized CD4 T Cells
Leveraging chromatin accessibility for transcriptional regulatory network inference in T Helper 17 Cells.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Treatment, Time
View SamplesType 1 regulatory T (Tr1) cells are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation. Overall design: Transcriptinal analysis of IL27-induced of WT, Irf1 KO, and Batf KO cells
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Cell line, Subject
View SamplesType 1 regulatory T (Tr1) cells are induced by the interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo . Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation.
Specimen part, Treatment
View SamplesGenomic analysis of axon pruning in Drosophila mushroom body neurons identifies the RNA-binding protein Boule as a negative regulator
Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning.
Age
View SamplesDrosophila mushroom body (MB) neurons undergo axon pruning during metamorphosis through a process of localized degeneration of specific axon branches. Developmental axon degeneration is initiated at the onset of metamorphosis by the pre-pupal rise in the steroid hormone ecdysone. This study identifies genes that alter their expression in MB neurons at the onset and early steps of axon pruning.
Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning.
Age
View SamplesThis study identifies genes that show EcR-dependent gene expression in MB neurons at the onset of axon pruning.
Genomic analysis of Drosophila neuronal remodeling: a role for the RNA-binding protein Boule as a negative regulator of axon pruning.
Age
View SamplesInterferon gamma treatment of macrophages results in hundreds if not thousands of alterations in gene expression and an antiviral state being established in these cells. Little is known about relationship between transcript synthesis, abundance and decay in macrophages during the first hours after interferon gamma treatment and how these factors influence the antiviral cellular phenotype.
An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway.
Age, Specimen part
View Samples