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Spatially resolved proteomics via tissue expansion

Author

Listed:
  • Lu Li

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Cuiji Sun

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake Institute for Advanced Study)

  • Yaoting Sun

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Zhen Dong

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Runxin Wu

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Xiaoting Sun

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake Institute for Advanced Study)

  • Hanbin Zhang

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake Institute for Advanced Study)

  • Wenhao Jiang

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Yan Zhou

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Xufeng Cen

    (Zhejiang University School of Medicine)

  • Shang Cai

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine)

  • Hongguang Xia

    (Zhejiang University School of Medicine
    The First Affiliated Hospital, Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Yi Zhu

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Tiannan Guo

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Kiryl D. Piatkevich

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake Institute for Advanced Study)

Abstract

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity of biological samples, however, it remains technically challenging due to the complexity of the tissue microsampling techniques and mass spectrometry analysis of nanoscale specimen volumes. Here, we describe a spatially resolved proteomics method based on the combination of tissue expansion with mass spectrometry-based proteomics, which we call Expansion Proteomics (ProteomEx). ProteomEx enables quantitative profiling of the spatial variability of the proteome in mammalian tissues at ~160 µm lateral resolution, equivalent to the tissue volume of 0.61 nL, using manual microsampling without the need for custom or special equipment. We validated and demonstrated the utility of ProteomEx for streamlined large-scale proteomics profiling of biological tissues including brain, liver, and breast cancer. We further applied ProteomEx for identifying proteins associated with Alzheimer’s disease in a mouse model by comparative proteomic analysis of brain subregions.

Suggested Citation

  • Lu Li & Cuiji Sun & Yaoting Sun & Zhen Dong & Runxin Wu & Xiaoting Sun & Hanbin Zhang & Wenhao Jiang & Yan Zhou & Xufeng Cen & Shang Cai & Hongguang Xia & Yi Zhu & Tiannan Guo & Kiryl D. Piatkevich, 2022. "Spatially resolved proteomics via tissue expansion," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34824-2
    DOI: 10.1038/s41467-022-34824-2
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    References listed on IDEAS

    as
    1. Ruedi Aebersold & Matthias Mann, 2016. "Mass-spectrometric exploration of proteome structure and function," Nature, Nature, vol. 537(7620), pages 347-355, September.
    2. Paul D. Piehowski & Ying Zhu & Lisa M. Bramer & Kelly G. Stratton & Rui Zhao & Daniel J. Orton & Ronald J. Moore & Jia Yuan & Hugh D. Mitchell & Yuqian Gao & Bobbie-Jo M. Webb-Robertson & Sudhansu K. , 2020. "Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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    Cited by:

    1. Yat Ho Chan & Koralege C. Pathmasiri & Dominick Pierre-Jacques & Maddison C. Hibbard & Nannan Tao & Joshua L. Fischer & Ethan Yang & Stephanie M. Cologna & Ruixuan Gao, 2024. "Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Simon Davis & Connor Scott & Janina Oetjen & Philip D. Charles & Benedikt M. Kessler & Olaf Ansorge & Roman Fischer, 2023. "Deep topographic proteomics of a human brain tumour," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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