Single‐cell transcriptomics stratifies organoid models of metabolic dysfunction‐associated steatotic liver disease

• DOI: 10.15252/embj.2023113898
• Publication Date: 2023-11-14T14:51:39Z
• Authors: Anja Hess; Stefan D Gentile; Amel Ben Saad; Raza‐Ur Rahman; Tim Habboub; Daniel S Pratt; Alan C Mullen
• Keywords: Organoid; Hepatic stellate cell; Steatohepatitis; Liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of morbidity with limited treatment options. Thus, accurate in vitro systems to test new therapies are indispensable. While recently, human organoid models have emerged assess disease, systematic evaluation their translational potential still missing. Here, we evaluated MASLD, comparatively testing induction three conditions: oleic acid, palmitic and TGF-β1. Through single-cell analyses, find that all induce inflammatory signatures, but only TGF-β1 promotes collagen production, fibrosis, hepatic stellate cell expansion. In striking contrast, acid ameliorates fibrotic signatures reduces the population. Linking data from each model gene expression associated MASLD progression further demonstrates more robustly inflammation fibrosis. Our findings highlight importance stratifying by clinical progression, provide reference benchmark future injury models, allow us study evolving steatohepatitis, HSC susceptibility dynamic, multi-lineage system.