Sphingolipids control dermal fibroblast heterogeneity

Laura Capolupo, Irina Khven, Alex R Lederer, Luigi Mazzeo, Galina Glousker, Sylvia Ho, Francesco Russo, Jonathan Paz Montoya, Dhaka R Bhandari, Andrew P Bowman, Shane R Ellis, Romain Guiet, Olivier Burri, Johanna Detzner, Johannes Muthing, Krisztian Homicsko, François Kuonen, Michel Gilliet, Bernhard Spengler, Ron M A HeerenG Paolo Dotto, Gioele La Manno, Giovanni D'Angelo

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

Human cells produce thousands of lipids that change during cell differentiation and can vary across individual cells of the same type. However, 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 with single-cell transcriptomics. We found that the cell-to-cell variations of specific lipid metabolic pathways contribute 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. Therefore, cell-to-cell lipid heterogeneity affects the determination of cell states, adding a new regulatory component to the self-organization of multicellular systems.

Original languageEnglish
Article numbereabh1623
Number of pages14
JournalScience
Volume376
Issue number6590
DOIs
Publication statusPublished - 15 Apr 2022

Keywords

  • Fibroblasts/metabolism
  • Humans
  • Metabolic Networks and Pathways
  • Skin
  • Sphingolipids/chemistry
  • Transcriptome
  • REGENERATION
  • TISSUE
  • IDENTIFICATION
  • MASS-SPECTROMETRY
  • ORGANIZATION
  • VARIABILITY
  • INHIBITION
  • SINGLE-CELL ANALYSIS
  • EXPRESSION
  • LIPID EXTRACTION

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