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Open AccessCholangiocyte organoids to study drug-induced injury
Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated me...
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Article
Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance
Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. The...
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Open AccessModelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells
Immunotherapy with immune checkpoint inhibitors (ICIs) is being explored to improve cholangiocarcinoma (CCA) therapy. However, it remains difficult to predict which ICI will be effective for individual patient...
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Open AccessKinome profiling of cholangiocarcinoma organoids reveals potential druggable targets that hold promise for treatment stratification
Cholangiocarcinoma is a rare but lethal cancer of the biliary tract. Its first-line treatment is currently restricted to chemotherapy, which provides limited clinical benefit. Kinase inhibitors targeting oncog...
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Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids
Fatty liver disease has grown into a major global health burden, attributed to multi-factors including sedentary lifestyle, obesogenic diet and prevalence of metabolic disorders. The lack of robust experimenta...
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Open AccessPrecancerous liver diseases do not cause increased mutagenesis in liver stem cells
Inflammatory liver disease increases the risk of develo** primary liver cancer. The mechanism through which liver disease induces tumorigenesis remains unclear, but is thought to occur via increased mutagene...
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Open AccessLong-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis
Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during developme...
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Open AccessHuman extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease
The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. Thi...
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Open AccessPrime editing for functional repair in patient-derived disease models
Prime editing is a recent genome editing technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct the vast majority of genetic defects. Here, we develop prime e...
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Open AccessLGR5 marks targetable tumor-initiating cells in mouse liver cancer
Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are thought to be the main drivers for disease progression and treatment resistance across various cancer types. Identifying and targeting these rare c...
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Open AccessUltra-thin fluorocarbon foils optimise multiscale imaging of three-dimensional native and optically cleared specimens
In three-dimensional light microscopy, the heterogeneity of the optical density in a specimen ultimately limits the achievable penetration depth and hence the three-dimensional resolution. The most direct appr...
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Open AccessLipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells
Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is in...
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Tissue-specific mutation accumulation in human adult stem cells during life
Stem cells of the liver, colon and small intestine gradually accumulate mutations throughout life at a similar rate even though cancer incidence varies greatly among these tissues.