Single-cell spatial proteomics maps human liver zonation patterns and their vulnerability to disruption in tissue...

Area of Science:

• Proteomics
• Cell Biology
• Systems Biology

Background:

• Understanding protein distribution in tissue architecture is key to deciphering organ function in health and disease.
• Spatially resolved proteome analysis provides insights into cellular organization and function.

Purpose of the Study:

• To apply single-cell Deep Visual Proteomics for spatially resolved proteome analysis in native liver tissue.
• To develop a framework for investigating protein gradients and larger clinical cohorts.
• To create a comprehensive spatial map of the human hepatic proteome.

Main Methods:

• Single-cell Deep Visual Proteomics applied to native liver tissue.
• Development of a framework for strategic cell selection and continuous protein gradient mapping.
• Analysis of hundreds of isolated hepatocytes from 18 individuals.

Main Results:

• Generated a comprehensive spatial map of the human hepatic proteome, identifying ~2,500 proteins per cell.
• Approximately half of identified proteins showed zonated expression patterns.
• Disrupted liver architecture led to widespread loss of protein zonation, particularly affecting pericentral proteins.
• Cross-species comparison revealed conserved metabolic functions and human-specific liver zonation features.

Conclusions:

• Established a broadly applicable framework for spatial proteomics analyses along tissue gradients.
• Provided a comprehensive, open-access resource of human liver organization.
• Demonstrated the importance of protein zonation for liver function and its susceptibility to architectural disruption.