Ultrahighly Sensitive in Situ Metabolomic Imaging for Visualizing Spatiotemporal Metabolic Behaviors

摘要

A sensitive and simultaneous analytical technique fornvisualizing multiple endogenous molecules is now stronglynrequired in biological science. Here, we show the applicabilitynof a matrix-assisted laser desorption ionizationnmass spectrometry (MALDI-MS) system for getting chemicallyndiverse metabolite profiles on a single-mammalianncell. This ultrahighly sensitive MALDI-MS techniquenenabled a spatially resolved detection of a broad range ofnmetabolites including nucleotides, cofactors, phosphorylatednsugars, amino acids, lipids, and carboxylic acids innnormal mouse brain tissue with their unique distributions.nFurthermore, a combination of MS imaging andnmetabolic pathway analysis of a rat transient middlencerebral artery occlusion model visualized a spatiotemporalnbehavior of metabolites in the central metabolicnpathway regulated by an ischemia reperfusion. Thesenfindings highlight potential applications of an in situnmetabolomic imaging technique to visualize spatiotemporalndynamics of the tissue metabolome, which willnfacilitate biological discovery in both preclinical andnclinical settings.