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WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [24hr. Bulk]

ABSTRACT: WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [24hr. Bulk]

PROVIDER: PRJNA1180100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31174716_1.fastq.gz	Fastqsanger.gz
	SRR31174716_2.fastq.gz	Fastqsanger.gz
	SRR31174717_1.fastq.gz	Fastqsanger.gz
	SRR31174717_2.fastq.gz	Fastqsanger.gz
	SRR31174718_1.fastq.gz	Fastqsanger.gz

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WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [24hr. Bulk]

Project description:Biliary obstruction and cholangiocyte hyperproliferation are important features of cholangiopathies affecting the large extrahepatic bile ducts (EHBD). The mechanisms underlying obstruction-induced cholangiocyte proliferation in the EHBD remain poorly understood. Developmental pathways, such as WNT signaling, have been implicated in regulating injury responses in many tissues, including the liver and bile ducts. To investigate the contribution of WNT signaling to the EHBD cholangiocyte proliferative response to obstructive injury, we conducted a comprehensive study using complementary in vivo and in vitro models with pharmacologic interventions and computational approaches. To model obstruction, we used bile duct ligation (BDL) in mice. Human and mouse biliary organoids and mouse biliary explants were used to investigate the effects of WNT activation and inhibition in vitro. We observed a rapid upregulation of WNT ligand expression associated with increased biliary proliferation following obstruction. Cholangiocytes were identified as both WNT ligand-expressing cells and WNT responsive cells. Inhibition of WNT signaling decreased cholangiocyte proliferation in vivo and in vitro, while activation increased proliferation. WNT proliferative effects on cholangiocytes were β-catenin-dependent. Our studies suggest that cholangiocyte-derived WNT ligands can activate canonical WNT signaling to induce proliferation after obstructive injury. These findings implicate the WNT pathway in injury-induced cholangiocyte proliferation within the EHBD.

2025-02-12 | GSE280724 | GEO

WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [scRNA-seq]

Project description:Biliary obstruction and cholangiocyte hyperproliferation are important features of cholangiopathies affecting the large extrahepatic bile duct (EHBD). The mechanisms underlying obstruction-induced cholangiocyte proliferation in the EHBD remain poorly understood. Developmental pathways, such as WNT signaling, have been implicated in regulating injury responses in many tissues, including the liver and bile ducts. To investigate the contribution of WNT signaling to the EHBD cholangiocyte proliferative response to obstructive injury, we conducted a comprehensive study using complementary in vivo and in vitro models with pharmacologic interventions and computational approaches. To model obstruction, we used bile duct ligation (BDL) in mice. Human and mouse biliary organoids and mouse biliary explants were used to investigate the effects of WNT activation and inhibition in vitro. We observed a rapid upregulation of WNT ligand expression associated with increased biliary proliferation following obstruction. Cholangiocytes were identified as both WNT ligand-expressing cells and WNT responsive cells. Inhibition of WNT signaling decreased cholangiocyte proliferation in vivo and in vitro, while activation increased proliferation. WNT proliferative effects on cholangiocytes were β-catenin-dependent. Our studies suggest that cholangiocyte-derived WNT ligands can activate canonical WNT signaling to induce proliferation after obstructive injury. These findings implicate the WNT pathway in injury-induced cholangiocyte proliferation within the EHBD.

2025-02-12 | GSE280889 | GEO

WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice

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WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice

Project description:WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice

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Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

Project description:Cholangiocyte organoids provide a powerful tool for characterizing bile duct epithelium and expanding cholangiocytes for tissue engineering purposes. However, this involves invasively obtained tissue-biopsies via surgery which is not preferential and limits the patient-specific capacities of these cultures. To overcome this, organoid culture were initiated from minimal invasive bile-samples obtained during routine clinical procedures. Characterization revealed that these bile-cholangiocyte organoids originate from the extrahepatic bile duct and are capable to repopulate human extrahepatic bile duct scaffolds. With this, bile duct tissue engineering as well as personalized disease modelling is in sight.

2020-11-19 | GSE156519 | GEO

WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [scRNA-seq]

Project description:WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice [scRNA-seq]

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Comparison of gene expression similarity between mouse extrahepatic bile duct and pancreatic duct epithelia and organoids prepared from these epithelia.

Project description:By RNA sequencing we found that extrahepatic bile duct organoids and pancreatic duct organoids have similar gene expression signatures compared with duct epithelia.

2023-06-06 | GSE196394 | GEO

Comparison of extrahepatic cholangiocyte organoids and freshly isolated common bile duct cholangiocytes

Project description:Despite the impact of bile duct disorders, treatment options remain very limited. Poor access to biliary tissue and restrictions in long-term culture or significant expansion of primary cholangiocytes have posed major challenges for research in the field. These limitations have so far precluded large scale experiments such as transcriptomic and genome-wide analyses which are urgently needed to better understand biliary physiology and pathophysiology. To address this issue, we have developed a novel system for the isolation and propagation of primary cholangiocytes from the extrahepatic bile ducts. The resulting Extrahepatic Cholangiocyte Organoids (ECOs) maintain their genetic stability, transcriptomic profile and function over long term culture and are compatible with regenerative medicine applications such as biliary reconstruction. We established a novel protocol for the isolation and propagation of primary cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs). The aim of this experiment was to provide in depth characterisation of the transcriptome of ECOs during long term culture. We compare the transcriptome of ECOs cultured for 1 passage (P1), 10 passages (P10) and 20 passages (P20) with freshly isolated primary cholangiocytes from the common bile duct. Embryonic Stem Cells (ES) cells are used as a negative control=

2017-07-04 | E-MTAB-4591 | biostudies-arrayexpress

WNT signaling contributes to the extrahepatic bile duct proliferative response to obstruction in mice.

Project description:Biliary obstruction and cholangiocyte hyperproliferation are important features of cholangiopathies affecting the large extrahepatic bile duct (EHBD). The mechanisms underlying obstruction-induced cholangiocyte proliferation in the EHBD remain poorly understood. Developmental pathways, including WNT signaling, are implicated in regulating injury responses in many tissues, including the liver. To investigate the contribution of WNT signaling to obstruction-induced cholangiocyte proliferation in the EHBD, we used complementary in vivo and in vitro models with pharmacologic interventions and transcriptomic analyses. To model obstruction, we used bile duct ligation (BDL) in mice. Human and mouse biliary organoids and mouse biliary explants were used to investigate the effects of WNT activation and inhibition in vitro. We observed an upregulation of WNT ligand expression associated with increased biliary proliferation following obstruction. Cholangiocytes were identified as both WNT ligand-expressing and WNT-responsive cells. Inhibition of WNT signaling decreased cholangiocyte proliferation in vivo and in vitro, while activation increased proliferation. WNT effects on cholangiocyte proliferation were β-catenin dependent, and we showed a direct effect of WNT7B on cholangiocyte growth. Our studies suggested that cholangiocyte-derived WNT ligands can activate WNT signaling to induce proliferation after obstructive injury. These findings implicate the WNT pathway in injury-induced cholangiocyte proliferation within the EHBD.

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Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

Project description:Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

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