ArticleNature cell biology2019
Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes.
Article in Nature cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- Liver organoids: From fabrication to application in liver diseases.Frontiers in physiology · 2022Pooled it
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Article
- Translating Pharmacology from Animal Models to Organoids: Advancing Predictive Human Biology in Drug Discovery.Stem cell reviews and reports · 2026Review
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026Review
- Applications and limitations of pluripotent stem cell-derived liver organoids.Chinese medical journal · 2026Review
- Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Expansion of human hepatocytes and their application in three-dimensional culture and genetic manipulation.Nature protocols · 2025Article
- 3D-bioprinted liver cancer models derived from primary hepatocytes for simulating cancer initiation and drug screening.Hepatology communications · 2025Article
- The application of liver cancer organoids in tumour precision medicine: A comprehensive review.iLIVER · 2025Review
- Tumor organoids in immunotherapy: from disease modeling to translational research.Journal for immunotherapy of cancer · 2025Review
- Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers.Scientific reports · 2025Article
- State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Precision models in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Emerging biotechnologies for engineering liver organoids.Bioactive materials · 2025Review
- Mitochondrial alterations and signatures in hepatocellular carcinoma.Cancer metastasis reviews · 2025Review
- Rational design matrix materials for organoid development and application in biomedicine.Regenerative biomaterials · 2025Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors.
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Abstract
Human liver cancers, including hepatocellular carcinomas and intra-hepatic cholangiocarcinomas, are often diagnosed late with poor prognosis. A better understanding of cancer initiation could provide potential preventive therapies and increase survival. Models for studying human liver cancer initiation are largely missing. Here, using directly reprogrammed human hepatocytes (hiHeps) and inactivation of p53 and RB, we established organoids possessing liver architecture and function. HiHep organoids were genetically engineered to model the initial alterations in human liver cancers. Bona fide hepatocellular carcinomas were developed by overexpressing c-Myc. Excessive mitochondrion-endoplasmic reticulum coupling induced by c-Myc facilitated hepatocellular carcinoma initiation and seemed to be a target of preventive treatment. Furthermore, through the analysis of human intra-hepatic cholangiocarcinoma-enriched mutations, we demonstrate that the RAS-induced lineage conversion from hepatocytes to intra-hepatic cholangiocarcinoma cells can be prevented by the combined inhibition of Notch and JAK-STAT. Together, hiHep organoids represent a system that can be genetically manipulated to model cancer initiation and identify potential preventive therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.