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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Proteogenomics uncovers critical elements of host response in bovine soft palate epithelial cells following in vitro infection with foot-and-mouth disease virus (FMDV)

ABSTRACT: The pathogen and host factors that contribute to the establishment of foot-and-mouth disease virus (FMDV) persistence are currently not understood. Using primary bovine soft palate multilayers in combination with RNA sequencing, we analyzed the transcriptional responses during acute and persistent FMDV infection.

INSTRUMENT(S): Ion Torrent S5 XL

ORGANISM(S): Bos taurus

SUBMITTER: Florian Pfaff

PROVIDER: E-MTAB-7605 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Proteogenomics uncovers critical elements of host response in bovine soft palate epithelial cells following in vitro infection with foot-and-mouth disease virus (FMDV)

Project description:: Foot-and-mouth disease (FMD) is the most devastating disease of cloven-hoofed livestock, with a crippling economic burden in endemic areas and immense costs associated with outbreaks in free countries. Foot-and-mouth disease virus (FMDV), a picornavirus, will spread rapidly in naïve populations, reaching morbidity rates of up to 100% in cattle. Even after recovery, over 50% of cattle remain subclinically infected and infectious virus can be recovered from the nasopharynx. The pathogen and host factors that contribute to FMDV persistence are currently not understood. Using for the first time primary bovine soft palate multilayers in combination with proteogenomics, we analyzed the transcriptional responses during acute and persistent FMDV infection. During the acute phase viral RNA and protein was detectable in large quantities and in response hundreds of interferon-stimulated genes (ISG) were overexpressed, mediating antiviral activity and apoptosis. Although the number of pro-apoptotic ISGs and the extent of their regulation decreased during persistence, some ISGs with antiviral activity were still highly expressed at that stage. This indicates a long-lasting but ultimately ineffective stimulation of ISGs during FMDV persistence. Furthermore, downregulation of relevant genes suggests an interference with the extracellular matrix that may contribute to the skewed virus-host equilibrium in soft palate epithelial cells.

2019-01-17 | PXD012242 | Pride

Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency

Project description:Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cells (MSCs) towards adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic MSC-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and we propose they function as guardians of mesenchymal multipotency.

2019-02-07 | E-MTAB-6840 | biostudies-arrayexpress

Identification of novel STAT6-regulated proteins in mouse B cells by comparative transcriptome and proteome analysis

Project description:IL-4/STAT6-regulated transcriptome and proteome were compared in primary B cells isolated from wild-type and STAT6-deficient mice. B cells were purified from the spleen and stimulated in vitro with anti-CD40 and LPS or anti-IgM-F(ab)2 in the presence or absence of IL-4. Transcriptome analysis was performed with oligonucleotide microarrays. Global relative quantification of proteins was achieved by gel-enhanced label-free liquid chromatography/mass spectrometry (LC/MS). Hierarchical clustering and principal component analysis revealed that IL-4-induced changes of the transcriptome were almost completely dependent on STAT6. In contrast, the quantitative proteome analysis revealed that the expression of many IL-4-regulated proteins changes even in the absence of STAT6. The top 75 proteins with changes in abundance levels induced by IL-4 in a STAT6-dependent manner were also found to be regulated at the transcriptional level. Most of these proteins were not previously known to be regulated by STAT6 in B cells. We confirmed the MS-based quantitative proteome data by flow cytometric and Western blot analysis of selected proteins. This study provides a framework for further functional characterization of STAT6-regulated proteins in B cells that might be involved in germinal center formation and class switch recombination.

2017-03-06 | PXD005224 | Pride

RNA-Seq from midgut of Ornithodoros moubata after feeding and infection with Borrelia duttonii

Project description:The tick midgut is the main tissue involved in blood feeding and the first organ to have contact with pathogens ingested through the blood meal. We characterized the early transcriptional changes in the midgut of O. moubata in the unfed, engorged and Borrelia duttonii-infected state. The aim is to identify transcripts that are differentially expressed in the respective physiological state.

2022-03-14 | E-MTAB-11507 | biostudies-arrayexpress

The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

Project description:Marek's disease virus (MDV) belongs to the alphaherpesviruses and is the causative agent of fatal T cell lymphomas in chickens. Aftermaths of MDV infections lead to substantial losses in poultry industry and there is evidence that MDV constantly evolves towards higher virulence. This study takes a detailed look at the very first step of the viral life cycle in the host: the infection of B cells. Recently, it has become possible to culture and infect primary chicken B cells ex vivo, enabling us to apply those cells to RNAseq analysis. Here, we provide novel insights into MDV gene expression profiles and post-transcriptional modifications of this important poultry pathogen in its primary target cells for lytic replication. Remarkably enough, we could detect a novel hypothetical MDV gene, identify multicistronic transcripts and previously unannotated splice forms. These findings lay the foundation for future research on MDV replication and pathogenesis and the developed bioinformatics pipeline can be easily transferred to other herpesviruses or large DNA viruses to identify unknown transcript isoforms and associated motifs.

2019-03-19 | E-MTAB-7772 | biostudies-arrayexpress

Whole-genome methylation profiling of monocytes and alveolar-like monocyte-derived macrophages from healthy controls and NSAID-exacerbated respiratory disease (N-ERD) patients

Project description:NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of AERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in N-ERD pathogenesis despite their presence in the nasal mucosa of N-ERD patients. Using a genome-wide methylomics approach, we identified persistent differences in monocytes and alveolar-like monocyte-derived macrophages (aMDM) between N-ERD patients and healthy controls. These were correlated with differentially expressed genes (DEGs) results from our whole transcriptome (RNAseq) analysis, available at: E-MTAB-7965 We isolated monocytes from venous blood and compared them to 7-days in vitro-differentiated aMDM. Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until genomic DNA isolation and genome-wide methylomics analysis. Three data analyses were performed. Analyses 1 and 2 compared differentially methylated positions (DMPs) and regions (DMRs) between N-ERD and healthy monocytes or aMDM, respectively. Analysis 3 compared the N-ERD vs. healthy-specific differences between both cell types.

2020-07-31 | E-MTAB-8065 | biostudies-arrayexpress

mRNAseq of human sputum macrophages and alveolar-like monocyte-derived macrophages of healthy controls and NSAID-exacerbated respiratory disease (N-ERD) patients

Project description:NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of N-ERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in N-ERD pathogenesis despite their presence in the nasal mucosa of N-ERD patients. Using a global transcriptomic approach, we identified systemic and local changes in macrophages between N-ERD patients and healthy controls. We isolated macrophages from induced sputum (sMac) and compared them to 7-days in vitro-differentiated, alveolar-like monocyte-derived macrophages (aMDM). Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until RNA isolation and RNAseq. Since sMac yield of healthy controls was low, we pooled RNA of three donors (= sample S1) but excluded the data from subsequent analyses. Thus Analysis 1 shows the intra-group comparison of N-ERD sMac vs. N-ERD aMDM. In a second analysis (Analysis 2), we compared N-ERD aMDM vs. healthy control aMDM for transcriptome differences present in monocyte (blood)-derived cells.

2020-06-30 | E-MTAB-7965 | biostudies-arrayexpress

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