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<p>Identifying the spatial distributions
of biomolecules in tissue is crucial for understanding integrated function.
Imaging Mass Spectrometry (IMS) allows simultaneous mapping of thousands of
biosynthetic products such as lipids but has needed a means of identifying
specific cell-types or functional states to correlate with molecular
localization. We report here advances starting from identity marking with a
genetically encoded fluorophore. The fluorescence emission data were integrated
with IMS data through multimodal image processing with advanced registration
techniques and data-driven image fusion. In an unbiased analysis of spleens,
this integrated technology enabled identification of ether lipid species
preferentially enriched in germinal centers. We propose that this use of genetic
marking for microanatomical regions of interest can be paired with molecular
information from IMS for any tissue, cell-type, or activity state for which
fluorescence is driven by a gene-tracking allele and ultimately with outputs of
other means of spatial mapping.</p>
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