Lipid signatures and inter-cellular heterogeneity of naive and lipopolysaccharide-stimulated human microglia-like cells

Microglia are non-neuronal cells, which are residing in the central nervous system and are known to play an important role in health and disease. We investigated lipidomic phenotypes of human naive and stimulated microglia-like cells by atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI). With lateral resolutions between 5 m and 1.5 m, we were able to chart lipid compositions of individual cells, enabling to differentiate cell lines and stimulation conditions. This allowed us to reveal local lipid heterogeneities in naive and lipopolysaccharide (LPS)-stimulated cells. We were able to identify individual cells with elevated triglyceride (TG) levels and could show that the number of these TG-enriched cells increased with LPS stimulation as a hallmark for a proinflammatory phenotype. Additionally, observed local abundance alterations of specific phosphatidylinositols (PIs) indicate a cell specific regulation of the PI metabolism.