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Challenges in Spatial Metabolomics and Proteomics for Functional Tissue Unit and Single-Cell Resolution
Kevin J Zemaitis1, Ljiliana Paša-Tolić2
1Analytical Chemistry Staff Scientist, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Seminars in Nephrology
|April 22, 2025
Summary
Advanced mass spectrometry imaging now routinely maps metabolites and proteins in tissues, revealing metabolic insights and disease connections. Further development and standardization of these spatial omics techniques promise deeper understanding of complex diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Analytical Chemistry
Background:
- Mass spectrometry imaging (MSI) has advanced significantly over the past decade.
- MSI enables routine spatial measurements of hundreds of metabolites and thousands of proteins within tissues.
Purpose of the Study:
- To overview developments in mass spectrometry imaging over the last decade.
- To highlight case studies of MSI applications in deciphering metabolic events and phenotypes.
- To discuss challenges and future directions for spatial omics, particularly at the single-cell level in mammalian kidneys.
Main Methods:
- Review of mass spectrometry imaging techniques and applications.
- Analysis of case studies demonstrating metabolite, protein, and proteoform measurements in tissues.
- Discussion of multidisciplinary approaches and technological advancements in spatial omics.
Main Results:
- Spatial measurements of metabolites and proteins are now feasible at the level of functional tissue units, approaching single-cell resolution.
- MSI experiments trace metabolic events and connect genetic and metabolic networks defining phenotypes.
- Commercial availability of MSI platforms is increasing.
Conclusions:
- Spatial omics techniques, particularly MSI, offer powerful tools for understanding complex biological systems and diseases.
- Addressing challenges in data analysis, harmonization, and quality control is crucial for wider adoption.
- Further integration of these techniques, especially at the single-cell level, will yield significant insights into mammalian kidney function and disease.

