​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology.

ABSTRACT: Liver organoids have emerged as an innovative three-dimensional model system that effectively recapitulates the structural and functional complexities of human liver tissue, addressing limitations of traditional two-dimensional culture systems. This study presents a comprehensive temporal proteomic characterization of iPSC-derived human liver organoids (iHLOs) by profiling 5,736 proteins across their four developmental stages, Days 7, 15, 30, and 45, to identify optimal timepoints for drug metabolism and toxicological applications. The analysis revealed that Day 30 represents the peak of functional maturity, marked by the highest expression of key-metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4), along with cholangiocyte-specific proteins and hepatic metabolic enzymes. Functional

SUBMITTER: Yang S 

PROVIDER: S-EPMC12824400 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature