Abstract

Human cells produce thousands of lipids that change during cell differentiation and can vary across individual cells of the same type. Yet, we are only starting to characterize the function of these cell-to-cell differences in lipid composition. Here we measured the lipidomes and transcriptomes of individual human dermal fibroblasts by coupling high-resolution mass spectrometry imaging to single-cell transcriptomics. We find that the cell-to-cell variation of specific lipid metabolic pathways contributes to the establishment of cell states involved in the organization of skin architecture. Sphingolipid composition is shown to define fibroblast subpopulations with sphingolipid metabolic rewiring driving cell state transitions. Thus cell-to-cell lipid heterogeneity affects the determination of cell states adding a new regulatory component to the self-organization of multicellular systems. [https://meet.goto.com/384576885]