Cell-type-resolved proteomic analysis of the human liver.

BACKGROUND & AIMS: The human liver functions through a complex interplay between parenchymal and non-parenchymal cells. Mass spectrometry-based proteomic analysis of intact tissue has provided an in-depth view of the human liver proteome. However, the predominance of parenchymal cells, i.e. hepatocytes, means that the total tissue proteome mainly reflects hepatocyte expression. Here, we therefore set out to analyze the proteomes of the major parenchymal and non-parenchymal cell types in the human liver. METHODS: We applied quantitative label-free proteomic analysis on the major cell types of the human liver, i.e. hepatocytes, liver endothelial cells, Kupffer cells, and hepatic stellate cells. RESULTS: We identified 9791 proteins, revealing distinct protein expression profiles across cell types, whose in vivo relevance was shown by the presence of cell-type-specific proteins. Analysis of proteins related to the immune system indicated that mechanisms of immune-mediated liver injury include the involvement of several cell types. Further, in-depth investigation of proteins related to the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of xenobiotics showed that ADMET-related tasks are not exclusively confined to hepatocytes, and that non-parenchymal cells may contribute to drug transport and metabolism. CONCLUSIONS: Overall, the data we provide constitutes a unique resource for exploring the proteomes of the major types of human liver cells, which will facilitate an improved understanding of the human liver in health and disease.