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

Johannes Krumm, Keisuke Sekine, Patroklos Samaras, Agnieska Brazovskaja, Markus Breunig, Ryota Yasui, Alexander Kleger, Hideki Taniguchi, Mathias Wilhelm, Barbara Treutlein, J. Gray Camp, Bernhard Kuster

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Article number110604
JournalCell Reports
Volume38
Issue number13
DOIs
StatePublished - 29 Mar 2022

Keywords

  • 2D versus 3D differentiation
  • CP: Cell biology
  • CP: Stem cell research
  • hepatocyte differentiation
  • post-translational modifications
  • proteomics
  • stem cell-derived organoids

Fingerprint

Dive into the research topics of 'High temporal resolution proteome and phosphoproteome profiling of stem cell-derived hepatocyte development'. Together they form a unique fingerprint.

Cite this