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Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [scRNA-seq]

ABSTRACT: Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [scRNA-seq]

PROVIDER: PRJNA842769 | ENA |

REPOSITORIES: ENA

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Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases.

Project description:Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases.

| PRJNA842765 | ENA

Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [scRNA-seq]

Project description:Diseases of the biliary epithelium (cholangiopathies) are an important cause of morbidity and mortality. Their pathogenesis and treatment remain unclear, in part because of the lack of disease models relevant to humans. 3D biliary organoids hold great promise, however the inaccessibility of their apical pole, and the presence of extracellular matrix (EBM) limit their experimental application. Here we show that when b integrin signaling is inhibited, either by removing the EMC or using blocking antibodies, biliary organoids revert their polarity and expose the apical membrane. Functional, immunohistochemical and TEM studies, along with bulk and single cell transcriptomic demonstrate that organoids in this novel 3D configuration, are less heterogeneous, show increased biliary differentiation, and decreased expression of stem cell markers. This model can be used to study bile transport, interactions with microbial agents, epithelial permeability, cross-talk with other liver and immune cell types and the effect of matrix changes on the biliary epithelium.

2023-09-21 | GSE204959 | GEO

Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [bulk RNA-seq]

2023-09-21 | GSE204958 | GEO

Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [bulk RNA-seq]

Project description:Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases [bulk RNA-seq]

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Cell-matrix interactions control biliary organoids polarity,architecture and differentiation and can be exploited to improve modelling of biliary diseases.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-21 | GSE204960 | GEO

Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia.

Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.

2021-10-25 | GSE186444 | GEO

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

Project description:Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands (PBGs) of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly more than ten-fold dilated PBGs following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

2022-12-05 | GSE220054 | GEO

mRNA expression profiling of ERCP biliary brushings of malignant biliary strictures

Project description:Identification of differential gene expression uging endoscopic biliary brushings Bile duct brishings of benign biliary strictures and malignant biliary strictures, samples snap frozen in liquid nitrogen

2012-03-01 | E-GEOD-34166 | biostudies-arrayexpress

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Project description:We present cisTopic, a probabilistic framework to simultaneously discover co-accessible enhancers and stable cell states from sparse single-cell epigenomics data (http://github.com/aertslab/cistopic). On a compendium of single-cell ATAC-seq datasets from differentiating hematopoietic cells, brain, and transcription-factor perturbation dynamics, we demonstrate that topic modelling can be exploited for a robust identification of cell types, enhancers, and relevant transcription factors. cisTopic provides insight into the mechanisms underlying regulatory heterogeneity within cell populations.

2019-02-18 | GSE114557 | GEO

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