Similar Datasets
Project description:Pentachlorophenol (PCP) is a highly toxic pesticide that was first introduced in the 1930s. The a-proteobacterium Sphingobium chlorophenolicum, which was isolated from PCP-contaminated sediment, has assembled a metabolic pathway capable of mineralizing PCP. Interestingly, this pathway produces four toxic intermediates, which include a chlorinated benzoquinone that is a potent alkylating agent and three chlorinated hydroquinones that produce reactive oxygen species and benzoquinones upon reaction with O2. We sought to identify how the cell tolerates the onslaught of toxic effects associated with these intermediates. RNA-Seq and Tn-Seq were used to probe the response of S. chlorophenolicum to PCP as well as the stresses associated with its exposure and degradation. The results demonstrate that PCP exposure causes dissipation of the proton-motive force and perturbation of the cell envelope, and the downstream intermediates cause oxidative stress. However, the transcriptional response to PCP degradation far exceeds what is actually needed and, for many genes, is actually counter-productive. Prevention of PCP degradation by deletion of the transcriptional regulator, pcpR, increases growth rate in rich medium. These data suggest that, although PCP degradation allows access to a novel nutrient, the benefit of degrading it depends upon the availability of other resources. When resources are abundant, the detrimental effects of the toxic intermediates may outweigh the benefit of the carbon and energy that can be obtained by degrading PCP. However, when resources are scarce, degradation of PCP may provide access to a novel source of carbon and energy as well as detoxification of this anthropogenic pollutant.
2018-11-01 | GSE114148 | GEO
Project description:Pentachlorophenol (PCP) is a highly toxic pesticide that was first introduced in the 1930s. The a-proteobacterium Sphingobium chlorophenolicum, which was isolated from PCP-contaminated sediment, has assembled a metabolic pathway capable of mineralizing PCP. Interestingly, this pathway produces four toxic intermediates, which include a chlorinated benzoquinone that is a potent alkylating agent and three chlorinated hydroquinones that produce reactive oxygen species and benzoquinones upon reaction with O2. We sought to identify how the cell tolerates the onslaught of toxic effects associated with these intermediates. RNA-Seq and Tn-Seq were used to probe the response of S. chlorophenolicum to PCP as well as the stresses associated with its exposure and degradation. The results demonstrate that PCP exposure causes dissipation of the proton-motive force and perturbation of the cell envelope, and the downstream intermediates cause oxidative stress. However, the transcriptional response to PCP degradation far exceeds what is actually needed and, for many genes, is actually counter-productive. Prevention of PCP degradation by deletion of the transcriptional regulator, pcpR, increases growth rate in rich medium. These data suggest that, although PCP degradation allows access to a novel nutrient, the benefit of degrading it depends upon the availability of other resources. When resources are abundant, the detrimental effects of the toxic intermediates may outweigh the benefit of the carbon and energy that can be obtained by degrading PCP. However, when resources are scarce, degradation of PCP may provide access to a novel source of carbon and energy as well as detoxification of this anthropogenic pollutant.
2018-11-01 | GSE114123 | GEO
Project description:Planar cell polarity PCP proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP proteins aretrafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in undifferentiated, but not differentiated, HC11 cells, which serve as a model for mammary lactogenic differentiation. Loss ofVangl2function results in upregulation of pathways related to STAT5 signaling.We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate recruitment of VANGL2 to specific DNA binding motifs, including one in theStat5apromoter. Knockdown KD ofVangl2in HC11 cells and primary mammary organoids results in upregulation ofStat5a,Ccnd1andCsn2, larger acini and organoids, and precocious differentiation; phenotypes rescued by overexpression ofVangl2, but notVangl2ΔNLS. Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.
2024-01-30 | GSE253793 | GEO
Project description:Pneumocystis pneumonia (PCP) is an opportunistic infectious disease prevalent in immunosuppressive host. Corticosteroids treatment is the most significant risk factor for HIV-negative patients with PCP, though little is known about how corticosteroids alters the host defense against Pneumocystis infection. In the present study, we used transcriptomic analysis to examine the immune response in the lung of dexamethasone-treated PCP mice and compare the immune reaction of them with those without dexamethasone treatment.
2016-05-03 | GSE80975 | GEO
Project description:We previously showed that abnormal morphology phenotype of ileal Paneth cells (Paneth cell phenotype [PCP]; as a surrogate for PC function) correlate with genetics, microbiota compositions, and aggressive outcome in Crohn’s disease (CD) patients. Given the shared genetics and clinical features between CD and ulcerative colitis (UC), we hypothesized that abnormal PCP also negatively modulates UC outcomes. As PCs has the highest density in the ileum, we further hypothesized that abnormal PCP from the terminal ileum could increase the risk of development of pouch complications after UC total colectomy and ileal pouch anal anastomosis (IPAA).
2025-01-01 | E-MTAB-12826 | biostudies-arrayexpress
Project description:Through chemical contamination of natural environments, microbial communities are exposed to many different types of chemical stressors; however, research on whole genome responses to this contaminant stress is limited. This study examined the transcriptome response of a common soil bacterium, Pseudomonas aeruginosa, to the common environmental contaminant pentachlorophenol (PCP). Cells were grown in chemostats at a low growth rate to obtain substrate-limited, steady-state, balanced-growth conditions. The PCP stress was administered as a continuous increase in concentration, and samples taken over time were examined for physiological function changes with whole cell acetate uptake rates (WAUR) and cell viability, and for gene expression changes using Affymetrix GeneChip technology and RT-PCR. Cell viability, measured by heterotrophic plate counts, showed a moderately steady decrease after exposure to the stressor, but WAURs did not change in response to PCP. In contrast to the physiological data, the microarray data showed significant changes in the expression of several genes. In particular, genes coding for multi-drug efflux pumps, including MexAB-OprM, were strongly upregulated. The upregulation of these efflux pumps protected the cells from the potentially toxic effects of PCP, allowing the physiological whole-cell function to remain constant. Experiment Overall Design: Cells of P. aeruginosa were grown in steady-state nutrient-limiting conditions using a minimal medium with acetate as the sole carbon source. PCP was added as a continuous input, and the samples were taken at timepoints corresponding to approximately 0.5, 1, and 2 generation times. Reactors were run at least in triplicate, and samples from duplicate WT reactors and a single RpoS- reactor were used for the microarrays. Gene expression is reported as the average fold-change associated with gene expression of PCP-shocked cells compared with the pre-PCP timepoint (0 hours) for the WT.
2008-06-13 | E-GEOD-5604 | biostudies-arrayexpress
Project description:Pentachlorophenol (PCP) as a widely used pesticide is also considered to be an endocrine disruptor. Molecular effects of chemicals with endocrine disrupting potential on soil invertebrates are largely unknown. Collembola (Folsomia candida) has been used as a model organism in ecotoxicity and in this study we explored the transcriptional expression changes of Folsomia candida in response to PCP contamination. A total of 92 genes were significantly differentially expressed at all exposure time and majority of them were found to be down-regulated. In addition to the transcripts encoding cytochrome P450s and transferase enzymes, chitin-binding protein was also identified in the list of common differentially genes. Analyses of Gene Ontology (GO) annotation and enrichment revealed that cell cycle related transcripts were significantly induced by PCP, indicating it can stimulated the cell proliferation in springtail as reported in human breast cancer cells. We also observed enrichment of functional terms related to steroid receptor and particularly twenty significant differential expressed genes involved in Chitin metabolism in response to PCP exposure. Combined with the confirmation by qPCR, our results appears that the adverse effects on reproduction of springtails after exposure to PCP can be attributed to a chemical-induced delay in the molting cycle and molting associated genes may serve as possible biomarkers for toxicological effects. In general, analysis of changes in the gene expression profiles of springtails in response to PCP exposure is useful for obtaining information on endocrine disruptor exposure of soil invertebrate and may contribute to the classification and risk assessment of relative chemicals.
2016-10-30 | GSE52893 | GEO
Project description:A detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required for better treatment options for a variety of chronic intestinal diseases, however, current models of ISC lineage hierarchy and segregation are still under debate. Here we report the identification of Lgr5+ ISCs that express Flattop (Fltp), a Wnt/planar cell polarity (PCP) reporter and effector gene. Functional analysis and lineage tracing revealed that Wnt/PCP-activated Fltp+ ISCs are primed towards either the enteroendocrine or Paneth cell lineage in vivo, while retaining self-renewal and multi-lineage capacity in vitro. Surprisingly, canonical Wnt/beta-catenin- and non-canonical Wnt/PCP-activated Lgr5+ ISCs are indistinguishable by the expression of stem-cell signature or secretory lineage-specifying genes, suggesting that lineage priming and cell-cycle exit is triggered at the post-transcriptional level by polarity cues and a switch of canonical to non-canonical Wnt signalling. Pseudotemporal ordering of targeted single-cell gene expression data allowed us to delineate the ISC differentiation path into enteroendocrine and Paneth cells. Strikingly, both lineages are directly recruited from ISCs via unipotent transition states, excluding the existence of formerly predicted bi- or multipotent secretory progenitors. Transitory cells that mature into Paneth cells are defined by label-retention and co-expression of stem cell and secretory lineage genes, indicating that these cells are the previously described Lgr5+ label-retaining cells (LRCs). Taken together, we identified the Wnt/PCP pathway as a new niche signal and polarity cue regulating stem cell fate. Active Wnt/PCP signalling represents one of the earliest events in ISC lineage priming towards the Paneth and enteroendocrine cell fate, preceding lateral inhibition and expression of secretory lineage-specifying genes. Thus, our findings provide a better understanding of the niche signals and redefine the mechanisms underlying ISC lineage hierarchy and segregation. Here we establish the Wnt/Planar cell polarity (PCP) gene Flattop (Fltp) as a unique marker for intestinal LRCs and their distinct secretory fate. We show that Fltp+ cells are characterized by a combined stem cell and secretory gene signature. A subset of Fltp+ cells is classified by label-retention and predominantly locates at position +4, indicative of quiescent stem cells. Strikingly, Fltp+ LRCs are specified by Wnt/PCP signaling in contrast to actively cycling stem cells that rely on the canonical Wnt/β-catenin pathway. In mice with disturbed Wnt/PCP signaling, the differentiation of enteroendocrine cells from LRCs is impaired. These findings establish Fltp as a novel marker for intestinal LRCs and implicate Wnt/PCP signaling in cell-cycle exit and commitment of ISCs to the secretory lineage. Taken together, we not only provide a marker to study LRCs in homeostatic and diseased conditions, but also identify the Wnt/PCP signaling pathway as a therapeutic target for colorectal cancer and metabolic disease.
2020-09-11 | GSE72112 | GEO
Project description:Pneumocystis is a life-threatening fungal pathogen frequently causing fatal pneumonia (PCP) in immunocompromised individuals with high mortality. Recently, B cells have been reported to play a crucial role in the pathogenesis of PCP through producing antibodies and activating CD4+ T cell response. Exosomes are nano-scale small extracellular vesicles (EVs) abundant of protein cargo and can mediate immune response during infectious disease. Here, using quantitative proteomic analysis coupled with bioinformatic analysis, we attempted to characterize exosomes derived from B lymphocytes in response to PCP. Also, the effects of B-cell exosomes on CD4+ T cell response and phagocytic function of macrophages were clarified. Briefly, 1701 proteins were identified from B-cell exosomes and the majority of them were reported in Vesiclepedia. 51 differentially expressed proteins of B-cell exosomes were found in response to PCP. They were mainly associated with immune response and transcription regulation. Particularly, a variety of histone components were enriched in B cell-derived exosomes when infected with Pneumocystis. Moreover, functional study revealed the pro-inflammatory profile of B-cell exosomes on CD4+ T cell response in PCP. Taken together, our results suggest the involvement of exosomes derived from B cells in cell-to-cell communication, providing new information on the function of B cells in response to PCP.
2022-04-26 | PXD030103 | Pride