High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development

ABSTRACT: Primary human hepatocytes are widely used to evaluate liver toxicity of drugs, but they are scarce and demanding to culture. Stem cell-derived hepatocytes are increasingly discussed as alternatives. To obtain a better appreciation of the molecular processes during the differentiation of induced pluripotent stem cells into hepatocytes, we employ a quantitative proteomic approach to follow the expression of 9,000 proteins, 12,000 phosphorylation sites, and 800 acetylation sites over time. The analysis reveals stage-specific markers, a major molecular switch between hepatic endoderm versus immature hepatocyte-like cells impacting e.g. metabolism, the cell cycle, kinase activity, and the expression of drug transporters. Comparing the proteomes of 2D and 3D-derived hepatocytes to fetal and adult liver, indicate a fetal-like status of the in vitro models and lower expression of important ADME/Tox proteins. The collective data enable constructing a molecular roadmap of hepatocyte development that serve as a valuable resource for future research.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Liver, Stem Cell

SUBMITTER: Johannes Krumm  

LAB HEAD: Bernhard Kuster

PROVIDER: PXD027439 | Pride | 2022-04-01

REPOSITORIES: Pride