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Sup:EasySCP Unveils Extensive Liver Zonation at Single-cell Proteomics Resolution

ABSTRACT: The widespread adoption of single-cell proteomics (SCP) in biology has been limited by complex workflows and reliance on specialized instrumentation. Here we present EasySCP, a high-throughput and lossless method that integrates FACS-based single-cell sorting, an all-in-one, single-step digestion process in 384-well plates, and sensitive mass spectrometry. EasySCP identifies nearly 5,000 proteins from individual HEK293 cell. Applied to murine liver, EasySCP achieved spatially resolved proteomics profiling of hepatocytes zonation, detecting an average of 3,500 proteins per hepatocyte and uncovering zonation patterns for 3,277 out of 5,267 proteins, representing unprecedented depth and coverage in single-cell liver proteomics. Building on 215 conserved zonation markers, we further developed hepatocyte spatial status score (HSS) that enables accurately reconstruct liver zonation across single-cell and spatial multi-omics datasets. Together, our study introduces EasySCP, a broadly accessible tool for dissecting cellular heterogeneity at single-cell proteomics resolution in both healthy and disease states, effectively bridging the gap between transcriptomics and functional proteomics.

ORGANISM(S): Homo Sapiens

SUBMITTER: Bingbing Hao

PROVIDER: PXD075305 | iProX | Fri Mar 06 00:00:00 GMT 2026

REPOSITORIES: iProX

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