Dynamic human liver proteome atlas reveals functional insights into disease pathways

Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell-type resolution. Here, we quantify more than 10,000 proteins and 150,000 sequence-unique peptides across total liver, the major liver cell types, time-course of primary cell cultures and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serves as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver biopsies include signatures of stellate cell activation resembling liver cirrhosis, providing functional insights.