Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE204959 | GEO | 2023/09/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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: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 | GSE204958 | 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

Illumina Human Polycystic Liver Disease and Normal Biliary Stem Cell RNAseq

Project description:Background & aims: Polycystic liver disease (PLD) is an autosomal dominantly inherited disorder caused by mutations in genes such as PRKCSH and SEC63. It has been thought that cysts develop from biliary progenitor cells due to loss-of-heterozygosity (LOH), leading to aberrant proliferation or defects in differentiation. Cyst expansion can be suppressed by somatostatin analogues such as lanreotide. There is no human in vitro model available that truly recapitulates polycystic liver disease. We hypothesize that PLD progenitors can form bipotent liver organoids that carry key features of cyst development. To find gene expression differences between Human Polycystic Liver Disease and Normal Biliary Stem Cells. Methods: Cells from normal biliary duct (n=6), cyst biliary epithelium (n=60) and cyst fluid (n=31) were isolated and placed under conditions suitable for expansion of human adult liver stem cells. We analyzed genetic LOH, gene expression, differentiation capacity, response to lanreotide and cilium formation of these organoids. Results: Cholangiocytes from cyst biliary epithelium (47/60) and cyst fluid (9/31) proved capable of expanding as bipotent liver organoids. Multiple cyst organoids displayed LOH surrounding PRKCSH or SEC63 regions. Organoids formed cilia when proliferation was inhibited. Neither hepatocyte nor biliary differentiation of PLD organoids was impaired. RNAseq revealed no significantly dysregulated pathway in PLD organoids. Lanreotide significantly decreased expansion of liver organoids in comparison to negative control (197% ± 46% versus 547% ± 28%; p: 0.038). Conclusion & discussion: Biliary progenitor cells from patient cyst epithelium and fluid can expand into liver organoids. They recapitulate key characteristics of PLD, and are a promising human in vitro model for research, diagnostics and treatment of polycystic liver diseases and cholangiociliopathies.

2015-09-30 | GSE73579 | 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

Expression data from murine intrahepatic biliary organoids

Project description:Mutations of isocitrate dehydrogenase (IDH) 1 or 2 occur in 10-30% of intrahepatic cholangiocarcinomas (ICCs). However, their functional roles in biliary carcinogenesis are still unknown. We used microarrays to investigate how mutant IDH1 affect the gene expression of intrahepatic biliary organoids generated from normal murine liver.

2019-07-31 | GSE134760 | GEO

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

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

| PRJNA773792 | ENA

Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers

Project description:Liver transplantation is the only treatment option for patients with end-stage liver disease. However, a persistent disparity remains between supply and demand for donor organs suitable for transplantation, resulting in a waiting list mortality of up to 20%. This has resulted in an increasing use of high-risk grafts from suboptimal, extended criteria donors, including livers from donation after circulatory death (DCD) donors, and donors with significant comorbidities such as advanced age, diabetes mellitus and livers with high fat content. While cold storage remains sufficient for livers considered optimal for transplantation, ECD grafts are more vulnerable to cold ischemic damage, resulting in many of these grafts being rejected. As an alternative to cold storage, ex-situ normothermic machine perfusion (NMP) has become an increasingly popular method for preservation, transportation and assessment of ECD livers prior to transplantation. This allows for functional assessment of the graft and provides the opportunity to assess key processes that can be used to determine organ viability. The use of both hepatocellular and biliary viability criteria in selection of suboptimal livers from ECD donors has led to the successful transplantation of these grafts with a low incidence of post-transplant cholangiopathies. However, the mechanisms of biliary injury, and recovery thereof, following static cold storage remains poorly understood. Insight into these mechanisms may further improve preservation and selection of ECD livers. Therefore, we performed an in-depth proteomics analysis of bile samples collected from human ECD livers during NMP to identify potential mechanisms linked to biliary injury, function and regeneration over the course of the perfusion, and to assess whether biliary protein profiles can distinguish between transplantable and non-transplantable grafts.

2023-11-21 | PXD046355 | Pride

Expression data from murine intrahepatic biliary organoids

Project description:Expression data from murine intrahepatic biliary organoids

| PRJNA556348 | ENA

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

microRNA expression profiles in organoids derived from biliary tract carcinomas [MAA-17164_1]

Project description:In the present study, we established organoids using cancer and non-cancer tissues obtained from patients with biliary tract carcinomas and investigated compehensive microRNA expression profiles.

2019-03-15 | GSE112405 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data