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

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Dec 14, 2022
Source ID
10.1038/s41467-022-35367-2

Entities

People

  • Bo An
  • Chao Xue
  • Jianmin Wang
  • Jie Pu
  • Jun Qu
  • Min Ma
  • Ming Zhang
  • Sailee Rasam
  • Shichen Shen
  • Shihan Huo
  • Shuo Qian
  • Xiaoyu Zhu

Organizations

  • National Cancer Institute
  • National Heart, Lung, and Blood Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute on Aging
  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Finite Element Method (FEM) for solving Partial Differential Equations (PDEs)
  • Molecular and Cellular Biochemistry
  • Nanoscale Plasmonic Nanotechnology

Technology Areas

  • Biotechnology