Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity
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 imag...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54438-0 |
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| _version_ | 1850162855074070528 |
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| author | 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 Ruijun Tian |
| author_facet | 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 Ruijun Tian |
| author_sort | Yanfen Xu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-84bb96e4287a4cb4ab79555de049b9c7 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-84bb96e4287a4cb4ab79555de049b9c72025-08-20T02:22:26ZengNature PortfolioNature Communications2041-17232024-11-0115111810.1038/s41467-024-54438-0Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneityYanfen Xu0Xi Wang1Yuan Li2Yiheng Mao3Yiran Su4Yize Mao5Yun Yang6Weina Gao7Changying Fu8Wendong Chen9Xueting Ye10Fuchao Liang11Panzhu Bai12Ying Sun13Shengping Li14Ruilian Xu15Ruijun Tian16State 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 TechnologyState 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 TechnologyState 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 TechnologyState 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 TechnologyState 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 TechnologyDepartment of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterState 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 TechnologyState 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 TechnologyState 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 TechnologyState 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 TechnologyState 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 TechnologyState 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 TechnologyDepartment of System Biology, School of Life Sciences, Southern University of Science and TechnologyDepartment of System Biology, School of Life Sciences, Southern University of Science and TechnologyDepartment of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer CenterDepartment of Oncology, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen 518020, China, The First Affiliated Hospital, Southern University of Science and TechnologyState 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 TechnologyAbstract 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.https://doi.org/10.1038/s41467-024-54438-0 |
| spellingShingle | 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 Ruijun Tian Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity Nature Communications |
| title | Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| title_full | Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| title_fullStr | Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| title_full_unstemmed | Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| title_short | Multimodal single cell-resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| title_sort | multimodal single cell resolved spatial proteomics reveal pancreatic tumor heterogeneity |
| url | https://doi.org/10.1038/s41467-024-54438-0 |
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