Sphingolipid Control of Fibroblast Heterogeneity Revealed by Single-Cell Lipidomics

• DOI: 10.1101/2021.02.23.432420
• Publication Date: 2021-02-23T23:40:10Z
• Authors: Laura Capolupo; Irina Khven; Luigi Mazzeo; Galina Glousker; Francesco Russo; Jonathan Paz Montoya; Sylvia Ho; Dhaka R. Bhandari; Andrew P. Bowman; Shane R. Ellis; Romain Guiet; Johannes Muthing; Bernhard Spengler; Ron M.A. Heeren; Gian Paolo Dotto; Gioele La Manno; Giovanni D’Angelo
• Keywords: Sphingolipid; Multicellular organism; Cell type; Lipidome; Single-Cell Analysis

Human cells produce thousands of lipids that impact a wide range biological processes in ways we are only starting to characterize. The cellular composition changes during differentiation events and also varies across individual the same type. Yet, precise differences lipid directly affect cell phenotypes remain unknown. Here have measured lipidomes transcriptomes human dermal fibroblasts by coupling high-resolution mass spectrometry imaging single-cell transcriptomics. We found cell-to-cell variation specific metabolic pathways contributes establishment states involved wound repair skin cancer growth. Sphingolipid defined fibroblast subpopulations while sphingolipid rewiring drove state transitions. These data uncover role for heterogeneity determination reveal new regulatory component homeostasis self-organization multicellular systems.