Hormone correction of dysfunctional metabolic gene expression in stem cell-derived liver tissue

作者：Alvile Kasarinaite, Maria Jiménez Ramos, Mariana Beltran-Sierra, Elena F. Sutherland, Pedro Arede Rei, Meijiu Zhao, Ying Chi, Meryam Beniazza, Andrea Corsinotti, Timothy J. Kendall, Neil C. Henderson, Jonathan Fallowfield, Philippa T. K. Saunders, David C. Hay · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04238-0 · 被引用次数：7 · 研究领域：Liver Disease Diagnosis and Treatment、Liver physiology and pathology、Pancreatic function and diabetes

The increase in metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH) is a worldwide healthcare challenge. Heterogeneity between men and women in the prevalence and mechanisms of MASLD and MASH is related to differential sex hormone signalling within the liver, and declining hormone levels during aging. In this study we used biochemically characterised pluripotent stem cell derived 3D liver spheres to model the protective effects of testosterone and estrogen signalling on metabolic liver disease 'in the dish'. We identified sex steroid-dependent changes in gene expression which were protective against metabolic dysfunction, fibrosis, and advanced cirrhosis patterns of gene expression, providing new insight into the pathogenesis of MASLD and MASH, and highlighting new druggable targets. Additionally, we highlight gene targets for which drugs already exist for future translational studies.