This SuperSeries is composed of the SubSeries listed below.
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Age, Specimen part, Treatment
View SamplesHelicobacter pylori infection is associated with development of gastric adenocarcinoma in a subset of infected humans, especially those that develop an antecedent condition, chronic atrophic gastritis (ChAG) characterized by loss of acid-producing parietal cells. Studies in a gnotobiotic transgenic mouse model of ChAG, with an engineered ablation of parietal cells and an associated expansion of gastric epithelial progenitors (GEPs), have shown that a subset of GEPs is able to harbor intracellular collections of H. pylori. To better understand H. pyloris adaptation to ChAG, we sequenced the genomes of 24 isolates, obtained from 6 individuals, each sampled over a 4-year interval, as they maintained normal gastric histology, or progressed from normal histology to ChAG, or experienced worsening ChAG, or proceeded from ChAG to cancer. Analyses of gene content and single nucleotide polymorphisms (SNPs) demonstrated that H. pylori populations within study participants were largely clonal, and remarkably stable over the 4-year interval, regardless of disease state. Because they exhibited such broad inter-host variation (38.64.7 SNPs/1000bp of genome), and did not cluster according to host pathology, we sought to identify common functional properties by performing GeneChip studies of the responses of a cultured mouse gastric stem cell-like line (mGEPs) to infection with sequenced strains. The results yielded a shared 695-member set of genes differentially expressed after infection with ChAG-associated, but not normal or heat killed strains: 434 of these genes were also represented in dataset of responses to the cancer-associated strain. Ingenuity Pathway Analysis revealed that ChAG- and ChAG/cancer- associated responses were significantly enriched in genes associated with tumorigenesis in general, and gastric carcinogenesis in specific cases. Whole genome transcriptional profiling of a sequenced ChAG strain during mGEP infection disclosed a set of responses that included upregulation of hopZ, an adhesin belonging to a family of outer membrane proteins. Expression profiles of wild-type and hopZ strains revealed a number of pH-regulated genes affected by loss of HopZ, including HopP which binds sialylated glycans produced by GEPs in vivo. Genetic inactivation of hopZ produces a fitness defect in gnotobiotic transgenic mice but not their wild-type littermates. This study illustrates an approach for identifying GEP responses specific to ChAG, and bacterial genes important for survival in a gastric ecosystem that lacks parietal cells.
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Age, Specimen part, Treatment
View SamplesNeutrophils provide immune protection against pathogens but also may promote tissue injury in inflammatory diseases. Although neutrophils are generally considered as a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and the replenishment by newly released neutrophils from the bone marrow.
Neutrophil ageing is regulated by the microbiome.
Specimen part, Treatment
View SamplesWe demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification.
Specimen part
View SamplesIn this experiment we profiled the transcriptome of intestinal colonic epithelium and total colonic tissue of animals colonized with T.mu versus naïve littermate controls at different time points Overall design: Groups of three mice were inoculated with 2x106 highly purified Tritrichomonas musculis. Total tissue and epithelial cells were collected at 3 days, 14 days and 48 days after inoculation from three different mice. RNA was isolated and sequenced
Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome.
Specimen part, Subject
View SamplesTranscriptome analyses on seeds developed in different parental conditions
Effects of Parental Temperature and Nitrate on Seed Performance are Reflected by Partly Overlapping Genetic and Metabolic Pathways.
No sample metadata fields
View SamplesIn order to elucidate transcriptional and metabolic networks associated with Lys metabolism, we utilized developing seeds as a system in which Lys synthesis could be stimulated developmentally without application of chemicals and coupled this to a T-DNA insertion knockout mutation impaired in Lys catabolism. This seed-specific metabolic perturbation stimulated Lys accumulation starting from the initiation of storage reserve accumulation. Our results revealed that the response of seed metabolism to the inducible alteration of Lys metabolism was relatively minor, however, that which was observable operated in a modular manner. They also demonstrated that Lys metabolism is strongly associated with the operation of the TCA cycle, whilst largely disconnected from other metabolic networks. In contrast, the inducible alteration of Lys metabolism was strongly associated with gene networks, stimulating the expression of hundreds of genes controlling anabolic processes that are associated with plant performance and vigor, whilst suppressing a small number of genes associated with plant stress interactions. The most pronounced effect of the developmentally-inducible alteration of Lys metabolism was an induction of expression of a large set of genes encoding ribosomal proteins as well as genes encoding translation initiation and elongation factors, all of which are associated with protein synthesis. With respect to metabolic regulation, the inducible alteration of Lys metabolism was primarily associated with altered expression of genes belonging to networks of amino acids and sugar metabolism. The combined data are discussed within the context of network interactions both between and within metabolic and transcriptional control systems.
Deciphering transcriptional and metabolic networks associated with lysine metabolism during Arabidopsis seed development.
No sample metadata fields
View SamplesAlloplasmic lines provide a unique tool to study the nucleo-cytoplasmic interactions. Alloplasmic lines T183 and T195 were developed through the introgression of the cytoplasm from Aegilops uniaristata (T183) and Aegilops squarrosa (T195) in the nuclear background of Triticum aestivum cv. Chris. Alloplasmic line TH237 was produced introgressing the Hordeum chilense accession H7 cytoplasm into the nuclear background of Triticum aestivum accession T20. Fifty seeds for each sample in pots of 11 cm diameter and grown in controlled conditions under 600E m-2 s1 high light intensity in a daily regime of 12 h light at 22C and 12 h darkness at 15C. Plants were bulked from each pot and three biological replicate used for the transcriptomics Fully expanded second leaves were collected two weeks from sowing in the middle of the light period and used for transcriptomic analysis.
Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations.
Specimen part
View SamplesA prominent enzyme in organellar RNA metabolism is the exoribonuclease polynucleotide phosphorylase (PNPase), whose reversible activity is governed by the nucleotides diphosphate-inorganic phosphate ratio. In Chlamydomonas reinhardtii, PNPase regulates chloroplast transcript accumulation in response to phosphorus (P) starvation, and PNPase expression is repressed by the response regulator PSR1 under these conditions. Here, we investigated the role of PNPase in the Arabidopsis (Arabidopsis thaliana) P deprivation response by comparing wild-type and pnp mutant plants with respect to their morphology, metabolite profiles, and transcriptomes. We found that P-deprived pnp mutants develop aborted clusters of lateral roots, which are characterized by decreased auxin responsiveness and cell division, and exhibit cell death at the root tips. Electron microscopy revealed that the collapse of root organelles is enhanced in the pnp mutant under P deprivation and occurred with low frequency under P-replete conditions. Global analyses of metabolites and transcripts were carried out to understand the molecular bases of these altered P deprivation responses. We found that the pnp mutant expresses some elements of the deprivation response even when grown on a full nutrient medium, including altered transcript accumulation, although its total and inorganic P contents are not reduced. The pnp mutation also confers P status-independent responses, including but not limited to stress responses. Taken together, our data support the hypothesis that the activity of the chloroplast PNPase is involved in plant acclimation to P availability and that it may help maintain an appropriate balance of P metabolites even under normal growth conditions.
Abnormal physiological and molecular mutant phenotypes link chloroplast polynucleotide phosphorylase to the phosphorus deprivation response in Arabidopsis.
Age, Specimen part, Treatment
View SamplesSmall intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate. culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small-intestinal microbial diversity and small-intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment. Overall design: A host duodenal RNA sequencing study in conjuction with a microbial analysis of small bowel aspirates following dietary intervention to reduce fiber intake for 1 week. Aspirates were collected during research endoscopy and submtttied for for 16S microbial identification (european
Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.
Sex, Age, Specimen part, Disease stage, Subject, Time
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