biostudies-literatureZhu LTianjin Municipal Science and Technology ProgramNatural Science Foundation of Tianjin MunicipalityNational Natural Science Foundation of China112344https://www.ebi.ac.uk/biostudies/studies/S-EPMC12019286biostudies-literatureUnknown28(5)Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common chronic liver disease worldwide, and appropriate <i>in vitro</i> models are of great significance for investigating pathogenesis and drug screening of MASLD. In this study, human expandable cholangiocyte organoids were derived from adult stem cells of normal liver tissue. After differentiation, liver organoids (LOs) exhibited the functional characteristics and genomic features of mature hepatocytes. To induce steatosis, LOs were incubated with a gradient concentration oleic acid, and it was found that the model could recapitulate the development of lipid accumulation and inflammation. In addition, the drug sensitivity of the hepatic steatosis model was further verified through anti-steatosis drug testiiScienceModeling hepatic steatosis with human adult stem cell-derived liver organoids.PMC12019286TJWJ2023MS01221JCYBJ0005082204546TJWJ2023QN03421JCYBJC0032082372194TJWJ2021ZD002TJWJ2023QN028Han PYang YYang LZhu LZhang YLiu SZhao TWang ZTong WCui TWang LfalseModeling hepatic steatosis with human adult stem cell-derived liver organoids.Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common chronic liver disease worldwide, and appropriate <i>in vitro</i> models are of great significance for investigating pathogenesis and drug screening of MASLD. In this study, human expandable cholangiocyte organoids were derived from adult stem cells of normal liver tissue. After differentiation, liver organoids (LOs) exhibited the functional characteristics and genomic features of mature hepatocytes. To induce steatosis, LOs were incubated with a gradient concentration oleic acid, and it was found that the model could recapitulate the development of lipid accumulation and inflammation. In addition, the drug sensitivity of the hepatic steatosis model was further verified through anti-steatosis drug testi2025-01-01T00:00:00Z2025 May2026-05-26T20:11:20.888Z2025-07-11T03:05:55.174ZS-EPMC120192864027676210.1016/j.isci.2025.112344