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

Min Ma, Shihan Huo, Ming Zhang, Shuo Qian, Xiaoyu Zhu, Jie Pu, Sailee Rasam, Chao Xue, Shichen Shen, Bo An, Jianmin Wang and Jun Qu ()
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Min Ma: SUNY at Buffalo
Shihan Huo: SUNY at Buffalo
Ming Zhang: SUNY at Buffalo
Shuo Qian: SUNY at Buffalo
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
Bo An: SUNY at Buffalo
Jianmin Wang: Roswell Park Comprehensive Cancer Center
Jun Qu: SUNY at Buffalo

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35367-2

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