%0 Journal Article
%A Krumm, Johannes
%A Sekine, Keisuke
%A Samaras, Patroklos
%A Brazovskaja, Agnieška
%A Breunig, Markus
%A Yasui, Ryota
%A Kleger, Alexander
%A Taniguchi, Hideki
%A Wilhelm, Mathias
%A Treutlein, Barbara
%A Camp, J. Gray
%A Kuster, Bernhard
%+ Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000A-31FC-3
%R 10.1016/j.celrep.2022.110604
%7 2022-03-29
%D 2022
%8 29.03.2022
%* Review method: peer-reviewed
%X 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 two- (2D) and three-dimensional (3D)-derived hepatocytes with fetal and adult liver indicates 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 serves as a valuable resource for future research.
%K hepatocyte differentiation, 
2D versus 3D differentiation, 
stem cell-derived organoids, 
proteomics
post-translational modifications
%J Cell Reports
%V 38
%] 110604
%@ 22111247