Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity

Yanfen Xu, Xi Wang, Yuan Li, Yiheng Mao, Yiran Su, Yize Mao, Yun Yang, Weina Gao, Changying Fu, Wendong Chen, Xueting Ye, Fuchao Liang, Panzhu Bai, Ying Sun, Shengping Li, Ruilian Xu and Ruijun Tian ()
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Yanfen Xu: Southern University of Science and Technology
Xi Wang: Southern University of Science and Technology
Yuan Li: Southern University of Science and Technology
Yiheng Mao: Southern University of Science and Technology
Yiran Su: Southern University of Science and Technology
Yize Mao: Sun Yat-sen University Cancer Center
Yun Yang: Southern University of Science and Technology
Weina Gao: Southern University of Science and Technology
Changying Fu: Southern University of Science and Technology
Wendong Chen: Southern University of Science and Technology
Xueting Ye: Southern University of Science and Technology
Fuchao Liang: Southern University of Science and Technology
Panzhu Bai: Southern University of Science and Technology
Ying Sun: Southern University of Science and Technology
Shengping Li: Sun Yat-sen University Cancer Center
Ruilian Xu: Southern University of Science and Technology
Ruijun Tian: Southern University of Science and Technology

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Despite the advances in antibody-guided cell typing and mass spectrometry-based proteomics, their integration is hindered by challenges for processing rare cells in the heterogeneous tissue context. Here, we introduce Spatial and Cell-type Proteomics (SCPro), which combines multiplexed imaging and flow cytometry with ion exchange-based protein aggregation capture technology to characterize spatial proteome heterogeneity with single-cell resolution. The SCPro is employed to explore the pancreatic tumor microenvironment and reveals the spatial alternations of over 5000 proteins by automatically dissecting up to 100 single cells guided by multi-color imaging of centimeter-scale formalin-fixed, paraffin-embedded tissue slide. To enhance cell-type resolution, we characterize the proteome of 14 different cell types by sorting up to 1000 cells from the same tumor, which allows us to deconvolute the spatial distribution of immune cell subtypes and leads to the discovery of subtypes of regulatory T cells. Together, the SCPro provides a multimodal spatial proteomics approach for profiling tissue proteome heterogeneity.

Date: 2024
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DOI: 10.1038/s41467-024-54438-0

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