Poster #057
Modeling Genetic Risk for MASLD Using iPSC-Derived Hepatocytes
Mentors: Marisa Medina, PhD and Yuanyuan Qin, PhD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a common chronic liver condition linked to obesity and diabetes. It affects nearly 25% of adults and can progress to cirrhosis or liver failure, yet effective treatments remain limited. Genome-wide association studies have identified numerous genetic variants associated with MASLD, and polygenic risk scores (PRS) combine these variants to estimate individual disease risk. However, existing models do not capture the complexity of polygenic risk. This study uses patient-derived induced pluripotent stem cells (iPSCs) to model MASLD by stratifying lines based on MASLD-specific PRS. iPSCs in the highest and lowest PRS percentiles are differentiated into hepatocyte-like cells (iHeps), treated with oleate to induce steatosis, and analyzed for lipid accumulation via BODIPY staining and flow cytometry. We hypothesize that high-PRS iHeps will show greater lipid accumulation, reflecting genetic risk. This platform may improve our understanding of MASLD pathogenesis and support personalized therapeutic strategies.