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Proteomics01:33

Proteomics

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A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
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Author Spotlight: Universal Molecular Retention with 11-Fold Expansion Microscopy
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iPEX enables micrometre-resolution deep spatial proteomics via tissue expansion.

Fengxiang Wang1,2,3,4,5,6, Cuiji Sun2,3,4, Tianshu William Wu1,2,3,4,5,6

  • 1Westlake Four-Dimensional Dynamic Metabolomics (Meta4D) Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.

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|November 12, 2025
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Summary

We developed in situ imaging proteomics via expansion (iPEX), a new untargeted spatial proteomics tool. iPEX maps proteins in tissues at high resolution, revealing early Alzheimer's disease changes and lipid metabolism disruptions.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Increasing development of spatial omics technologies.
  • Need for untargeted protein localization at high spatial resolution and coverage.
  • Limitations in current methods for comprehensive spatial proteomics.

Purpose of the Study:

  • Introduce in situ imaging proteomics via expansion (iPEX) for untargeted spatial proteomics.
  • Achieve high spatial resolution and coverage for protein mapping in tissues.
  • Investigate early molecular changes in Alzheimer's disease models.

Main Methods:

  • Integration of isotropic tissue magnification with MALDI mass spectrometry imaging.
  • Application of iPEX to diverse tissues including retina, brain, intestine, and liver.
  • Analysis of protein expression and localization at micrometre scale.

Main Results:

  • iPEX provides scalable spatial resolution down to the micrometre scale with 10-100-fold increased sensitivity.
  • Construction of high-precision spatial proteomic maps, visualizing single-cell layers and structures.
  • Detection of 600-1,500 proteins at 1-5-µm effective pixel size across various tissues.
  • Identification of early mitochondrial aberrancy in 5xFAD Alzheimer's disease mouse models.
  • Downregulation of ACAA1, impacting long-chain polyunsaturated fatty acid biosynthesis, linked to neurodegeneration.

Conclusions:

  • iPEX is a powerful tool for untargeted spatial proteomics at micrometre resolution.
  • Revealed early molecular insights into Alzheimer's disease pathogenesis, including lipid metabolism.
  • Demonstrated broad applicability of iPEX across diverse biological samples and research areas.