Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1002769 | ENA |
REPOSITORIES: ENA
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Project description:The pathogenesis of primary sclerosing cholangitis (PSC) is unclear, although studies implicate IL-17A as an inflammatory mediator in this disease. However, a direct assessment of IL-17 signaling in PSC cholangiocytes is lacking. Cholangiocytes obtained from PSC and non-PSC patients by endoscopic retrograde cholangiography (ERC) were cultured as extrahepatic cholangiocyte organoids (ECO). The ECO were treated with vehicle or IL-17A and assessed by NanoString analysis, single cell RNA sequencing (scRNA-seq), and whole genome sequencing (WGS). The secretome was assessed by Olink analysis. Unsupervised clustering of all integrated scRNA-seq data identified 8 cholangiocyte clusters which did not differ between non-PSC and PSC ECO. However, PSC ECO cells demonstrated a much more robust response to IL-17 treatment, noted by an increased number of differentially expressed genes (DEG) after the treatment with IL-17A, compared to non-PSC ECO. After rigorous filtering, WGS identified the presence of somatic mutations that were shared between PSC ECO. However, no somatic mutations dysregulating genes in the IL-17 pathway were identified. The secretome of PSC ECO contained more abundant chemokines and cytokines under basal conditions and following IL-17A stimulation when compared to non-PSC ECO. In conclusion, PSC and non-PSC patient derived ECO respond differently to IL-17 stimulation regardless of mutational status, suggesting a change in epigenetic regulation and the implication of this pathway in the pathogenesis of PSC.
2024-01-29 | GSE239283 | GEO
Project description:Microplastic particles that occur in the environment are coated with different biomolecules forming an eco-corona on the particles' surface, which could consequently lead to a specific interaction of the constituents of the eco-corona with membrane receptors. To date, it is not fully understood how strong microplastic particles with and without an eco-corona bind to cellular membranes and which underlying mechanisms are responsible for cellular internalization. Here we analyzed the protein composition of two different eco-coronas (freshwater and saltwater) by LC-MS/MS.
2025-03-07 | PXD050078 | Pride