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Updated: Jun 6, 2025
A Streamlined Approach for Mass Spectrometry-Based Proteomics Using Selected Tissue Regions
Published on: April 18, 2025
Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity
Yanfen Xu1, Xi Wang1,2, Yuan Li1
1State Key Laboratory of Medical Proteomics and Shenzhen Key Laboratory of Functional Proteomics, Department of Chemistry and Research Center for Chemical Biology and Omics Analysis, School of Science and Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, China.
Spatial and Cell-type Proteomics (SCPro) enables single-cell spatial proteome analysis in complex tissues. This new method reveals thousands of protein alterations and discovers novel regulatory T cell subtypes within the pancreatic tumor microenvironment.
Area of Science:
- Proteomics
- Single-cell analysis
- Tissue microenvironment
Background:
- Integrating antibody-guided cell typing and mass spectrometry-based proteomics is challenging for rare cells in heterogeneous tissues.
- Existing methods struggle with spatial context and single-cell resolution for proteomic analysis.
Purpose of the Study:
- To introduce a novel multimodal spatial proteomics approach for characterizing tissue proteome heterogeneity with single-cell resolution.
- To overcome limitations in analyzing rare cells within complex tissue environments.
Main Methods:
- Spatial and Cell-type Proteomics (SCPro) combines multiplexed imaging, flow cytometry, and ion exchange-based protein aggregation capture.
- Automated dissection of up to 100 single cells guided by multi-color imaging of tissue slides.
- Proteomic characterization of up to 1000 sorted cells from 14 distinct cell types for enhanced resolution.
Main Results:
- SCPro successfully explored the pancreatic tumor microenvironment, revealing spatial alternations of over 5000 proteins.
- Enabled deconvolution of spatial distribution for immune cell subtypes.
- Led to the discovery of novel subtypes of regulatory T cells.
Conclusions:
- SCPro provides a powerful multimodal spatial proteomics approach for profiling tissue proteome heterogeneity.
- This method enhances understanding of cellular composition and spatial organization in tumors.
- Facilitates discovery of new cell subtypes and their spatial roles.
