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Modeling ischemic cholangiopathy in human cholangiocyte organoid for screening of novel cholangio-protective agents

ABSTRACT: Modeling ischemic cholangiopathy in human cholangiocyte organoid for screening of novel cholangio-protective agents

PROVIDER: PRJNA817199 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18356573_1.fastq.gz	Fastqsanger.gz
	SRR18356573_2.fastq.gz	Fastqsanger.gz
	SRR18356574_1.fastq.gz	Fastqsanger.gz
	SRR18356574_2.fastq.gz	Fastqsanger.gz
	SRR18356575_1.fastq.gz	Fastqsanger.gz

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Modeling ischemic cholangiopathy in human cholangiocyte organoid for screening of novel cholangio-protective agents

Project description:Ischemic cholangiopathy refers to biliary damage caused by disruption of blood supply in the peribiliary plexus. Detailed knowledge of ischemic cholangiopathy pathogenesis remains scarce due to the lack of appropriate in vitro models. We aimed to recapitulate ischemia-evoked biliary damage using human intrahepatic cholangiocyte organoids (ICOs) in vitro for the study of ischemic cholangiopathy and preclinical drug discovery. In our study, we found that ICOs can recapitulate ischemic cholangiopathy in vitro, featured by extensive apoptosis and reduced cell proliferation, which could be partially restored by reoxygenation. AAT is identified as a novel cholangiocellular protective agent by restoring proliferation and preventing apoptosis.

2022-11-01 | GSE198860 | GEO

Transcription profiling of undifferentiated human extrahepatic cholangiocyte organoids (ECOs)

Project description:3D cell culture systems (organoids), cultured from extrahepatic bile duct biopsies, resemble biliary epthelium (cholangiocytes) upon culture according to the protocol previously established for culturing intrahepatic cholangiocyte organoids from liver biopsies (Huch et al. Cell 2015). These extrahepatic cholangiocyte organoids (ECOs) in Canonical-Wnt culture conditions maintain their genetic stability, and transcription profile and can be maintained and propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 3 different ECO lines that were analyzed for their functional cholangiocyte ion-channels, involved in secreting a protective bicarbonate layer. It was shown that these data closely resemble the expression profile of intrahepatic cholangiocyte organoids (ICOs) as described by our group. Results of the ICOs are deposited in the EMBL-EBI ArrayExpress repository under number E-MTAB-9044.

2021-01-01 | E-MTAB-9807 | biostudies-arrayexpress

Transcription profiling of undifferentiated human liver-derived intrahepatic cholangiocyte organoids (ICOs)

Project description:3D cell culture systems (organoids), cultured from liver biopsies, resemble biliary epthelium (cholangiocytes) upon culture. These intrahepatic cholangiocyte organoids (ICOs) maintain their gentic stability, transcription profile and can be maintained propagated during long periods of culturing while still maintaining their functional properties. The data presented in this ArrayExpress submission contained micro array results of 6 from 15 different ICO lines that were analyzed for their functional cholangiocyte ion-channels, involved in secreting a protective bicarbonate layer. It was shown that these data closely resemble the expression profiles of extrahepatic cholangiocyte organoids (ECOs), previously described by Sampaziotis et al. and deposited in the EMBL-EBI ArrayExpress repository (E-MTAB-4591)

2020-07-31 | E-MTAB-9044 | biostudies-arrayexpress

LPS-induced systemic inflammation mediates a protective effect against ischemic injury via microglia

Project description:LPS-induced systemic inflammation mediates a protective action on ischemic injury via microglia. We used RNA sequencing analysis (RNA-seq) to gain molecular insights into microglia-mediated protection of cerebral infarction.

2023-12-19 | GSE244358 | GEO

Cholangiocyte organoid culture in hydrogels from decellularized liver tissue

Project description:Culture of human cholangiocyte organoids in hydrogels derived from healthy liver extracellular matrix (LECM) extracts prepared from decellularized human livers are evaluated in an effort to establish a platform for production of cholangiocyte organoids for clinical regenerative applications. Human intrahepatic cholangiocyte organoids (ICO) grown in hydrogels made from LECM are compared those grown in mouse tumor derived basement membrane extracts (BME). Culture was performed with amino acids labeled with stable heavy isotopes to enable separation of ECM from the hydrogels from that of the produced by the cells with mass spectrometry (MS). MS data were used to evaluate the protein production of ICO comparing the different hydrogel substrates. The study also contains evaluation of the properties of the hydrogel substrates and focuses on expansion and differentiation of the ICO.

2022-04-13 | PXD028417 | Pride

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.

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Modeling bile duct ischemia and reoxygenation injury in human cholangiocyte organoids for screening of novel cholangio-protective agents.

Project description:BackgroundIschemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models.MethodsTo recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by re-oxygenation at normal levels.FindingsICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis.InterpretationThese findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies.FundingDutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program "Regenerative Medicine 4D"; China Scholarship Council No. 201706230252.

| S-EPMC9826934 | biostudies-literature

Human branching cholangiocyte organoids recapitulate embryogenic bile duct development and provide an unique model to study biliary diseases. RNA-Seq

Project description:Although providing promising and unique tools for studying cholangiocytes, current tissue-derived cholangiocyte-organoid systems do not recapitulate the complex architecture of the intrahepatic bile ducts in vitro. Here, we report a new method for creating branching cholangiocyte organoids (BRCO) from human adult tissue to study the intrahepatic biliary tree and diseases. BRCOs self-organize into large complex tubular structures, while closely resembling primary cholangiocytes on a transcriptomic and functional level. They are capable of mimicking branching bile duct development as well as being used for studying diseases in which the biliary tree does not develop properly (Alagille Syndrome). Furthermore, we deliver evidence that our culture method allows for formation of complex cholangiocyte cancer (cholangiocarcinoma, CCA) organoids. These branching CCA organoids resemble the primary tumor more closely compared to previously published protocols as well as showing unique tumor-specific drug responses. In conclusion, our culture method allows for creation of novel (malignant) cholangiocyte-organoids to study the intrahepatic bile ducts.

2022-05-04 | GSE179599 | GEO

Human branching cholangiocyte organoids recapitulate embryogenic bile duct development and provide an unique model to study biliary diseases. scRNA-Seq

2022-05-04 | GSE179597 | GEO

RNA-seq of single cholangiocyte-derived organoids reveals high organoid-to-organoid variability

Project description:RNA-seq of single cholangiocyte-derived organoids reveals high organoid-to-organoid variability

| PRJNA847447 | ENA