Null
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB74045 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile, by means of whole transcriptome analysis, of peripheral blood mononuclear cells (PBMCs) derived from a healthy human donor and stimulated with a Pseudomonas aeruginosa phage PNM lysate, or P. aeruginosa strain 573. The PBMCs were stimulated for 20 h, followed by lysis of the cells and RNA extraction. In total, three stimulations were performed: control sample (i.e. not stimulated), P. aeruginosa phage PNM lysate and P. aeruginosa strain 573. Each stimulation was conducted in triplicate. The transcriptome analysis showed that the phage induce a clear immunological responses. Both pro- and anti-inflammatory genes were up-regulated in the PBMCs in the presence of the phage or its bacterial host. Our results indicate that bacteriophages might play a bigger role in the immune response then previously described and might have a broader effect than the clearing of bacterial infections alone, such as the suppression of the immune response to benefit their own survival.
2017-03-02 | GSE95573 | GEO
Project description:Endoplasmic reticulum (ER) and inflammatory stress responses are two pathophysiologic factors contributing to islet dysfunction and failure in Type 2 Diabetes (T2D). However, how human islet cells respond to these stressors and whether T2D-associated genetic variants modulate these responses is unknown. To fill this knowledge gap, we profiled transcriptional (RNA-seq) and epigenetic (ATAC-seq) remodeling in human islets exposed to ex vivo ER (thapsigargin) or inflammatory (IL-1β+IFN-γ) stress. 5,427 genes (~32%) were associated with stress responses; most were stressor-specific, including upregulation of genes mediating unfolded protein response (e.g. DDIT3, ATF4) and NFKB signaling (e.g. NFKB1, NFKBIA) in ER stress and inflammation respectively. Islet single-cell RNA-seq profiling revealed strong but heterogeneous beta cell ER stress responses, including a distinct beta cell subset that highly expressed apoptotic genes. Epigenetic profiling uncovered 14,968 stress-responsive cis-regulatory elements (CREs; ~14%), the majority of which were stressor-specific, and revealed increased accessibility at binding sites of transcription factors that were induced upon stress (e.g. ATF4 for ER stress, IRF8 for inflammation). Seventy-six stress-responsive CREs overlapped known T2D-associated variants, including 20 residing within CREs that were more accessible upon ER stress. Among these, we linked the rs6917676 T2D risk allele (T) to increased in vivo accessibility of an islet ER stress-responsive CRE and allele-specific beta-cell nuclear factor binding in vitro. We showed that MAP3K5, the only ER stress-responsive gene in this locus, promotes beta cell apoptosis. Consistent with its pro-apoptotic and putative diabetogenic roles, MAP3K5 expression inversely correlated with beta cell abundance in human islets and was upregulated in beta cells from T2D donors. Together, this study provides new genome-wide insights into human islet stress responses and putative mechanisms of T2D genetic variants.
2024-01-15 | GSE251910 | GEO
Project description:Type 2 diabetes (T2D) is associated with cardiovascular-renal complications and premature death. Although most patients with T2D are obese, not all obese individuals develop T2D. Thus, an understanding of the mechanistic relationships between obesity and T2D is crucial. In this study, using subcutaneous (SAT) and visceral adipose tissues (VAT) from obese individuals with or without T2D collected during metabolic surgery, integration of the transcriptomes and methylomes of VAT and SAT with publicly available tissue-specific regulatory networks, we discovered the close relation between T2D and inflammatory response in both SAT and VAT in obese individuals, although less differences were observed respectively in transcriptome or methylome. Specifically, a HOX gene family-enriched functional epigenetic sub-network in T2D-SAT, as well as a novel such sub-network was discovered, which involved multiple genes implicated in activation of obesity-induced inflammatory response. Our integrated approach of using biosamples, multi-omic data and public databases to understand complex diseases for discovery of novel biology, including biomarkers and drug targets, can be applied to diseases other than T2D and obesity.
2021-12-20 | GSE162166 | GEO
Project description:Genome sequencing of Staphylococcus hominis strains used in studying skin bacteriophages resistance mechanisms
| PRJEB67963 | ENA
Project description:Genome sequencing of Staphylococcus hominis strains used in studying skin bacteriophages resistance mechanisms
| PRJEB67984 | ENA
Project description:Genome sequencing of Staphylococcus hominis strains used in studying skin bacteriophages resistance mechanisms
| PRJEB67529 | ENA
Project description:Re-identifying the genome sequences of Staphylococcus hominis strains used in studying skin bacteriophages
| PRJEB68213 | ENA
Project description:Proinflammatory stimuli rapidly and globally remodel chromatin landscape, thereby enabling transcriptional responses. Yet, the mechanisms coupling chromatin regulators to the master regulatory inflammatory transcription factor NF-kB remain poorly understood. We report in human endothelial cells (ECs) that activated NF-kB binds to enhancers, provoking a rapid, global redistribution of BRD4 preferentially at super-enhancers, large enhancer domains highly bound by chromatin regulators. Newly established NF-kB super-enhancers drive nearby canonical inflammatory response genes. In both ECs and macrophages BET bromodomain inhibition prevents super-enhancer formation downstream of NF-kB activation, abrogating proinflammatory transcription. In TNFa-activated endothelium this culminates in functional suppression of leukocyte rolling, adhesion and transmigration. Sustained BET bromodomain inhibitor treatment of LDLr -/- animals suppresses atherogenesis, a disease process rooted in pathological vascular inflammation involving endothelium and macrophages. These data establish BET-bromodomains as key effectors of inflammatory response through their role in the dynamic, global reorganization of super-enhancers during NF-kB activation. ChIP-Seq for various transcription factors, RNA Polymerase II, and histone modifications in human endothelial cells
2014-09-29 | E-GEOD-53998 | biostudies-arrayexpress
Project description:Metabolic disorders impact adipose-derived stem cells (ASCs), which play a central role in adipose tissue (AT) homeostasis but might also regulate tumour microenvironments via paracrine signalling routes. Here, we aimed to determine whether type 2 diabetes (T2D) disturbs the protein secretome of human ASCs, and its potential relevance for their pro-tumoral activity. An untargeted proteomics approach by liquid chromatography coupled to tandem mass spectrometry was used to analyse the secretome of ASCs isolated from the subcutaneous AT of subjects with and without T2D. Out of 231 quantified proteins, 52 factors were found differentially secreted on T2D-ASCs. In silico studies revealed that only 46,7% of the total proteins identified used the conventional secretory pathway. Network analysis showed up-secreted factors in T2D were implicated in immune system processes, extracellular matrix organization and endoplasmic reticulum stress. We found that diabetic ASCs secretome increases some inflammatory-, invasiveness- and epithelial-to-mesenchymal transition-related markers in HepG2 cells, an effect that was blocked with an anti-SUB1 antibody. Remarkably, SUB1 neutralization also inhibited invasive capacities of HepG2 in response to T2D-ASCs secretome. Overall, our study demonstrates that T2D-ASCs show an aberrant protein secretome and although further studies will be needed to understand the pathogenic consequences of this disturbance, our findings suggest that SUB1 might serve as a novel molecular link in the interplay between ASCs and tumor cells.
2022-06-03 | PXD029829 | Pride
Project description:Endoplasmic reticulum (ER) and inflammatory stress responses are two pathophysiologic factors contributing to islet dysfunction and failure in Type 2 Diabetes (T2D). However, how human islet cells respond to these stressors and whether T2D-associated genetic variants modulate these responses is unknown. To fill this knowledge gap, we profiled transcriptional (RNA-seq) and epigenetic (ATAC-seq) remodeling in human islets exposed to ex vivo ER (thapsigargin) or inflammatory (IL-1β+IFN-γ) stress. 5,427 genes (~32%) were associated with stress responses; most were stressor-specific, including upregulation of genes mediating unfolded protein response (e.g. DDIT3, ATF4) and NFKB signaling (e.g. NFKB1, NFKBIA) in ER stress and cytokine-induced inflammation respectively. Islet single-cell RNA-seq profiling revealed strong but heterogeneous beta cell ER stress responses, including a distinct beta cell subset that highly expressed apoptotic genes. Epigenetic profiling uncovered 14,968 stress-responsive cis-regulatory elements (CREs; ~14%), the majority of which were stressor-specific, and revealed increased accessibility at binding sites of transcription factors that were induced upon stress (e.g. ATF4 for ER stress, IRF8 for cytokine-induced inflammation). Eighty-six stress-responsive CREs overlapped known T2D-associated variants, including 20 residing within CREs that were more accessible upon ER stress. Among these, we linked the rs6917676 T2D risk allele (T) to increased in vivo accessibility of an islet ER stress-responsive CRE and allele-specific beta cell nuclear factor binding in vitro. We showed that MAP3K5, the only ER stress-responsive gene in this locus, promotes beta cell apoptosis. Consistent with its pro-apoptotic and putative diabetogenic roles, MAP3K5 expression inversely correlated with beta cell abundance in human islets and was induced in beta cells from T2D donors. Together, this study provides new genome-wide insights into human islet stress responses and putative mechanisms of T2D genetic variants.
2024-01-15 | GSE251912 | GEO