MS-based spatial proteomics: deciphering tissue microenvironment by bridging MS imaging and large-scale proteomics

Alexandre Goossen, Laurine Lagache, Michel Salzet, Isabelle Fournier

Trends in Chemistry

https://doi.org/10.1016/j.trechm.2025.09.002

Abstract

Mass spectrometry (MS)-based spatial proteomics combines molecular profiling with histological context, allowing proteins and peptides to be mapped within tissues. Evolving from early immunostaining to advanced mass spectrometry imaging (MSI), multiplex immuno-MSI, and spatially resolved proteomics, this field now addresses significant challenges in biology and medicine. In this review, we outline various approaches and methodologies from foundational methods to recent advances including matrix-assisted laser desorption/ionization (MALDI) immunohistochemistry (IHC) and spatially resolved large-scale proteomics. Examples from oncology and neuroscience illustrate the growing impact of spatial proteomics, while emerging directions such as single-cell and subcellular workflows, tissue-expansion strategies, and integrated multi-omics foreshadow a future of comprehensive tissue atlases at unprecedented resolution.