% pubman genre = article @article{item_3375691, title = {{High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development}}, author = {Krumm, Johannes and Sekine, Keisuke and Samaras, Patroklos and Brazovskaja, Agnie{\v{s}}ka and Breunig, Markus and Yasui, Ryota and Kleger, Alexander and Taniguchi, Hideki and Wilhelm, Mathias and Treutlein, Barbara and Camp, J. Gray and Kuster, Bernhard}, language = {eng}, issn = {22111247}, doi = {10.1016/j.celrep.2022.110604}, year = {2022}, 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 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.}}, journal = {{Cell Reports}}, volume = {38}, eid = {110604}, }