Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1031602 | ENA |
REPOSITORIES: ENA
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Project description:Only recently, the natural gut microbiome of the model organism Caenorhabditis elegans has been described. C. elegans harbors a distinct gut microbiome that is shaped by environmental conditions, age, and host genotype. However, there is not much known about the genetic factors on the molecular level that the worm employs in order to keep its microbiota at bay. Previously, we have shown that TGFβ/BMP immune signaling is able to control the gut microbiome of C. elegans in particular in regards to Enterobacter species. We now aimed to identify the downstream targets of TGFβ/BMP immune signaling that implement the changes in microbiome composition. Hence, we exposed TGFβ mutants, dbl-1(nk3) and sma-3(e491), overexpression strain ctIs40 [dbl-1(+) + sur-5::GFP], and wild-type N2 to a synthetic microbiota community, CeMbio, and an E. coli OP50 control, and performed RNAseq. CeMbio is a collection of 12 diverse bacterial strains, previously isolated from wild C. elegans, C. elegans grown in microcosms, or substrates with C. elegans. Using the R packages edgeR and limma we are currently analyzing the data to understand the involvement of TGFβ/BMP signaling in host-microbiome interaction.
2023-10-31 | GSE186653 | GEO
Project description:Purpose: The goal of this study is to understand how dbl-1, which is made primarily in neurons, and hrg-7, which is exclusively made in the intestine, contribute to systemic heme homeostasis. Methods: mRNA profiles of late L4 dbl-1(nk3) and hrg-7(tm6801) mutant C. elegans fed OP50 E. coli or OP50 + 50µM heme were compared to mRNA profiles from wildtype (WT) broodmates. Profiles were generated with single-end 50 base reads obtained using Illumina’s HiSeq 2500. Bioinformatics quality control was performed followed by alignment of reads to the ce10 reference genome using Tophat2, version 2.1.0. We found differentially expressed genes using Cufflinks 2, version 2.2.1 with a cutoff of 0.05 on False Discovery Rate (FDR). Results: We found a substantial overlap of genes regulated by both dbl-1 and hrg-7, including 49 heme-responsive genes (hrgs) in low heme (OP50) and 11 hrgs in high heme (OP50 + 50µM). Additionally, our data indicate crosstalk between dbl-1 and hrg-7 signaling. dbl-1 directly regulates hrg-7 expression, while hrg-7 regulates three components of the dbl-1 signaling pathway. Conclusions: Our study demonstrates that communication between the neuron and intestine is essential for heme homeostasis. Specifically, we report that HRG-7 functions as a secreted signaling factor which communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate genes involved in heme homeostasis. Cellular requirements for heme are fulfilled by a cell’s internal capacity to synthesize its own heme in a cell-autonomous manner. However, growing evidence in vertebrates predicts that cellular heme levels in animals are not only maintained by heme synthesis, but also by distally located proteins that could signal systemic heme requirements to an inter-organ heme trafficking network through cell-nonautonomous regulation. Using C. elegans, a genetically and optically amenable animal model for visualizing heme-dependent signaling, we show that HRG-7, an aspartic protease homolog, mediates inter-organ signaling between the intestine and neuron. Loss of hrg-7 results in robust expression of intestinal heme importers and, remarkably, this occurs even under heme replete conditions when such transporters are not normally expressed. HRG-7 functions as a secreted signaling factor, independent of a functional enzymatic active site, and communicates intestinal heme status with extraintestinal tissues by integrating a DBL-1/BMP -dependent response from the neurons to transcriptionally regulate intestinal heme homeostasis. Given the evidence indicating that mechanisms of heme transport are conserved across metazoa, it is conceivable that the cell-nonautonomous signaling framework that we uncovered in C. elegans may have functional relevance for inter-organ regulation of iron and heme metabolism in humans.
2017-03-24 | GSE76455 | GEO
Project description:The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. The changes in cellular composition is driven by immune cell derived cytokines. Here we use signature cytokines of different type of immune responses applied to small intestinal organoids to model how different immune responses affect intestinal epithelial development. Simplified, IL-13 represents type II immunity against infections such as parasites and IL-22 represents type III immunity against infections such as extracellular bacterial infections. 10 ng/mL of IL-13 and IL-22 was added for 72 hours after splitting. Furthermore, we have found BMP signaling to be important in regulating the cellular differentiation induced by IL-13. We therefore added added a combination treatment with the activin receptor-like kinase 2 (ALK-2) signaling inhibitor Dorsomorphin homolog 1 (DMH1) in concentration of 5 uM. We find that ALK-2 signaling is crucial for IL-13 driven Tuft cell differentiation.
2022-05-08 | E-MTAB-9185 | biostudies-arrayexpress
Project description:The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. The changes in cellular composition is driven by immune cell derived cytokines. Here we investigate the response over time upon stimulation with 10 ng/mL of the cytokine Interleukin-13 (IL-13). The intestinal organoids were lyzed 48 hours after splitting and IL-13 was added 24h, 8h, 4h and 1h before lysis. Furthermore, we have found BMP signaling to be important in regulating the cellular differentiation induced by IL-13. We therefore added added a combination treatment with the activin receptor-like kinase 2 (ALK-2) signaling inhibitor Dorsomorphin homolog 1 (DMH1) in concentration of 5 uM in some samples 24 hours before lysis. We find that ALK-2 signaling is crucial for IL-13 driven Tuft cell differentiation.
2022-05-08 | E-MTAB-10455 | biostudies-arrayexpress
Project description:Compare the global gene expression profiles of Sma-6 and Dbl-1 in L4 stage C. elegans Experiment Overall Design: Sma-6 and Dbl-1 mutants compared
2009-08-09 | E-GEOD-15527 | biostudies-arrayexpress
Project description:Caenorhabditis elegans intestinal transcriptome
| PRJNA291676 | ENA
Project description:Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans
| PRJNA115703 | ENA
Project description:Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. We found that losing one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, results in hypersusceptibility to both P. aeruginosa and ToxA. We determined that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 PMK-1 MAPK signaling. Here we present the microarray data that was used to determine that (1) nipi-3 regulates immune gene expression and that (2) nipi-3 and pmk-1 regulate non-overlapping gene sets consistent with them functioning in parallel. We used microarray analysis to identify the genes regulated by nipi-3 and pmk-1 at the L4 stage.
2016-09-18 | GSE87052 | GEO
Project description:Compare the global gene expression profiles of Sma-6 and Dbl-1 in L4 stage C. elegans
2009-07-28 | GSE15527 | GEO
Project description:Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA impacts on the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the immune system in the absence of changes to the composition of this flora. In contrast, untargeted lipidomic analysis focusing on bacteria-derived lipid mediators revealed that sPLA2-IIA could profoundly alter the fecal lipidome. The data suggest that a singular protein, sPLA2-IIA, produces systemic effects on the immune system through its activity on the microbiota and its lipidome.
2021-11-25 | GSE189441 | GEO