Single cell spatial proteomics maps human liver zonation patterns and their vulnerability to fibrosis

Area of Science:

• Biochemistry
• Cell Biology
• Proteomics

Background:

• Understanding protein distribution in tissue architecture is key to organ function.
• Spatial proteome analysis provides insights into cellular organization.

Purpose of the Study:

• To create a spatial map of the human hepatic proteome using single-cell Deep Visual Proteomics.
• To investigate protein expression patterns and their disruption in liver fibrosis.

Main Methods:

• Applied single-cell Deep Visual Proteomics for spatially-resolved proteome analysis.
• Utilized a novel cell selection pipeline and protein gradient mapping framework.
• Analyzed hundreds of hepatocytes from 18 individuals and compared with mouse data.

Main Results:

• Generated a comprehensive spatial map of the human hepatic proteome.
• Identified zonated expression patterns for over half of the 2,500+ proteins analyzed per cell.
• Revealed conserved metabolic functions and human-specific liver zonation features across species.
• Observed widespread disruption of protein zonation in fibrotic liver samples, particularly affecting pericentral proteins.

Conclusions:

• Established a broadly applicable framework for spatial proteomics along tissue gradients.
• Provided a valuable resource for understanding human liver organization and disease.
• Highlighted the susceptibility of pericentral proteins to disruption in liver fibrosis.