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In-depth mapping of protein localizations in whole tissue by micro-scaffold assisted spatial proteomics (MASP)

Author

Listed:
  • Min Ma

    (SUNY at Buffalo
    Roswell Park Comprehensive Cancer Center)

  • Shihan Huo

    (SUNY at Buffalo)

  • Ming Zhang

    (SUNY at Buffalo
    New York State Center of Excellence in Bioinformatics & Life Sciences)

  • Shuo Qian

    (SUNY at Buffalo
    Roswell Park Comprehensive Cancer Center)

  • Xiaoyu Zhu

    (SUNY at Buffalo)

  • Jie Pu

    (SUNY at Buffalo)

  • Sailee Rasam

    (Jacobs School of Medicine and Biomedical Sciences, SUNY at Buffalo)

  • Chao Xue

    (SUNY at Buffalo)

  • Shichen Shen

    (SUNY at Buffalo
    New York State Center of Excellence in Bioinformatics & Life Sciences)

  • Bo An

    (SUNY at Buffalo
    Department of DMPK, Huiyu (Seacross) Pharmaceuticals Ltd)

  • Jianmin Wang

    (Roswell Park Comprehensive Cancer Center)

  • Jun Qu

    (SUNY at Buffalo
    Roswell Park Comprehensive Cancer Center
    New York State Center of Excellence in Bioinformatics & Life Sciences)

Abstract

Accurate, in-depth mapping of proteins on whole-tissue levels provides comprehensive insights into the spatially-organized regulatory processes/networks in tissues, but is challenging. Here we describe a micro-scaffold assisted spatial proteomics (MASP) strategy, based on spatially-resolved micro-compartmentalization of tissue using a 3D-printed micro-scaffold, capable of mapping thousands of proteins across a whole-tissue slice with excellent quantitative accuracy/precision. The pipeline includes robust tissue micro-compartmentalization with precisely-preserved spatial information, reproducible procurement and preparation of the micro-specimens, followed by sensitive LC-MS analysis and map generation by a MAsP app. The mapping accuracy was validated by comparing the MASP-generated maps of spiked-in peptides and brain-region-specific markers with known patterns, and by correlating the maps of the two protein components of the same heterodimer. The MASP was applied in mapping >5000 cerebral proteins in the mouse brain, encompassing numerous important brain markers, regulators, and transporters, where many of these proteins had not previously been mapped on the whole-tissue level.

Suggested Citation

  • Min Ma & Shihan Huo & Ming Zhang & Shuo Qian & Xiaoyu Zhu & Jie Pu & Sailee Rasam & Chao Xue & Shichen Shen & Bo An & Jianmin Wang & Jun Qu, 2022. "In-depth mapping of protein localizations in whole tissue by micro-scaffold assisted spatial proteomics (MASP)," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35367-2
    DOI: 10.1038/s41467-022-35367-2
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    References listed on IDEAS

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    1. Guolan Lu & Naoki Nishio & Nynke S. Berg & Brock A. Martin & Shayan Fakurnejad & Stan Keulen & Alexander D. Colevas & Greg M. Thurber & Eben L. Rosenthal, 2020. "Co-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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    3. 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. 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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