MALDI-MSI-Guided Laser Capture Microdissection Coupled with MS for Integrated Spatial Multi-Omics in Mouse Brain
Byoung-Kyu Cho1,2, Jessica K Lukowski1, Minsoo Son1
1Mass Spectrometry Technology Access Center at McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.
Life (Basel, Switzerland)
|July 28, 2026
Summary
This study introduces a novel workflow combining mass spectrometry imaging and laser capture microdissection for spatial multi-omics. This method provides detailed molecular mapping and quantitative analysis of tissue regions, revealing insights into biological systems.
Area of Science:
- Biochemistry
- Molecular Biology
- Analytical Chemistry
Background:
- Spatial multi-omics analyzes biomolecules within their native spatial context.
- Mass spectrometry imaging (MSI) and laser capture microdissection coupled with mass spectrometry (LCM-MS) are key techniques for region-specific molecular analysis.
Purpose of the Study:
- To develop and validate an integrated matrix-assisted laser desorption/ionization (MALDI)-MSI-guided LCM-MS workflow for comprehensive spatial multi-omics profiling.
- To apply this workflow to mouse brain tissue for proof-of-principle validation.
Main Methods:
- Utilized MALDI-MSI to map metabolites and lipids in mouse brain tissue.
- Employed LCM to isolate cortex and hippocampus regions of interest (ROIs).
- Performed LC-MS/MS for metabolomics, lipidomics, and proteomics analysis on isolated ROIs.
Main Results:
- MALDI-MSI identified 387 putative metabolites and lipids with distinct distributions between cortex and hippocampus.
- LC-MS/MS analysis annotated 249 compounds with region-specific abundance patterns and identified over 3500 protein groups.
- Biological network analysis revealed associations between molecular pathways and region-specific phenotypes.
Conclusions:
- The developed MALDI-MSI-guided LCM-MS workflow enables integrated spatial multi-omics profiling and quantitative biomolecular analysis.
- This approach provides valuable insights into complex biological systems and spatial molecular organization.
