Language

English

Publication Date

5-1-2025

Journal

Nature Methods

DOI

10.1038/s41592-025-02664-9

PMID

40263584

PMCID

PMC12074994

PubMedCentral® Posted Date

4-22-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI). TEMI reaches single-cell spatial resolution without sacrificing voxel throughput and enables the profiling of hundreds of biomolecules, including lipids, metabolites, peptides (proteins), and N-glycans. Using TEMI, we mapped the spatial distribution of biomolecules across various mammalian tissues and uncovered metabolic heterogeneity in tumors. TEMI can be easily adapted and broadly applied in biological and medical research, to advance spatial multi-omics profiling.

Keywords

Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Animals, Mice, Humans, Single-Cell Analysis, Metabolomics, Mass spectrometry, Molecular imaging, Lipidomics, Lipidomics

Published Open-Access

yes

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