MALDI-imaging-guided transcriptomics
Spatial biology on cellular level is revolutionizing numerous fields, including ecology, pathophysiology and neurobiology. Understanding how microbial and eukaryotic cells interact via metabolic interactions is still a challenge. Enabling the study of cells within their tissue context, facilitates the exploration of tissue architecture, cell-to-cell interactions, and biomolecular dependencies. Spatial omics, particularly mass spectrometry imaging (MSI), offers a powerful method to uncover the spatial distribution of metabolites at a micrometer resolution. While the metabolome represents the final phenotype in the omics line, its comprehensive coverage remains challenging. Consequently, integrating spatial metabolomics with proteomics and transcriptomics proves benefitscial for analyzing active metabolic pathways. In this study, we employed a combination of spatial metabolomics and transcriptomics to investigate the metabolism of intracellular symbiotic bacteria in a marine invertebrate. The results demonstrate a proof of concept, illustrating that spatial metabolome analysis using MALDI-MSI, followed by guided dissection of cells and tissues for spatial transcriptomics, offers an in-situ view of host-microbe metabolism. This integrated approach holds tremendous potential for advancing our understanding of host-microbe interactions and may pave the way for novel strategies targeting the metabolism of host associated bacteria.