Challenges in Spatial Metabolomics and Proteomics for Functional Tissue Unit and Single-Cell Resolution.

In the last decade, advanced developments of mass spectrometry-based assays have made spatial measurements of hundreds of metabolites and thousands of proteins not only possible, but routine. The information obtained from such mass spectrometry imaging experiments traces metabolic events and helps decipher feedback loops across anatomical regions, connecting genetic and metabolic networks that define phenotypes. Herein we overview developments in the field over the past decade, highlighting several case studies demonstrating direct measurement of metabolites, proteins, and proteoforms from thinly sliced tissues at the level of functional tissue units, approaching single-cell levels. Much of this work is feasible due to multidisciplinary team science, and we offer brief perspectives on paths forward and the challenges that persist with adoption and application of these spatial omics techniques at the single-cell level on mammalian kidneys. Data analysis and reanalysis still pose issues that plague spatial omics, but many mass spectrometry imaging platforms are commercially available. With greater harmonization across platforms and rigorous quality control, greater adoption of these platforms will undoubtedly provide major insights in complex diseases.