In a recent study published in Nature Methods (Nunes et al., 2024), researchers developed a dual approach combining matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with imaging mass cytometry (IMC) to explore metabolic diversity at a single-cell level. This dual approach allowed the researchers to capture both metabolic and immunophenotypic profiles from the same tissue samples without disrupting spatial organization.
The study applied this technique to colorectal cancer tissue, focusing on how different cell types contribute to the metabolic environment of tumors. Using glycerophospholipids as indicators, the researchers observed unique metabolic profiles for cancer cells, stromal cells, and immune cells. For example, cancer cells exhibited elevated phosphatidylinositol levels, while immune cells had distinct phosphatidylcholine profiles. Such data points provide insights into how tumors modify their metabolism in response to immune activity, revealing relationships between cellular function and metabolic state that were previously undetectable.
Integrating MALDI-MSI with IMC also enabled the quantification of over 22 distinct cellular phenotypes, achieving high-dimensional single-cell analysis across tissue samples. The coregistration process aligned the mass spectrometry and cytometry images, allowing precise single-cell metabolic profiling and providing a more comprehensive view of cell-specific metabolism. The resulting data highlighted metabolic heterogeneity in the tumor microenvironment, offering potential targets for more personalized therapies.
This method’s capability to examine spatially resolved cellular metabolism at single-cell resolution has significant implications for cancer research, immunology, and beyond. By merging molecular and spatial information, this research opens doors for further study into the dynamic interactions within complex tissues, potentially leading to breakthroughs in precision medicine and targeted treatments. The innovative technique expands the toolkit for spatial omics, offering a powerful new approach to understanding cellular metabolism in diverse diseases.
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Reference
Nunes, J.B., Ijsselsteijn, M.E., Abdelaal, T. et al. Integration of mass cytometry and mass spectrometry imaging for spatially resolved single-cell metabolic profiling. Nat Methods 21, 1796–1800 (2024). https://doi.org/10.1038/s41592-024-02392-6
