Sphingolipids control dermal fibroblast heterogeneity

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2022-04, Vol.376 (6590), p.eabh1623-eabh1623
Main Authors: Capolupo, Laura, Khven, Irina, Lederer, Alex R, Mazzeo, Luigi, Glousker, Galina, Ho, Sylvia, Russo, Francesco, Montoya, Jonathan Paz, Bhandari, Dhaka R, Bowman, Andrew P, Ellis, Shane R, Guiet, Romain, Burri, Olivier, Detzner, Johanna, Muthing, Johannes, Homicsko, Krisztian, Kuonen, François, Gilliet, Michel, Spengler, Bernhard, Heeren, Ron M A, Dotto, G Paolo, La Manno, Gioele, D'Angelo, Giovanni
Format: Article
Language:English
Subjects:
Abnormalities
Biological membranes
Cell constituents
Cell differentiation
Cell fate
Composition
Constituents
Cytokines
Decisions
Differentiation (biology)
Energy metabolism
Extracellular matrix
Fibroblast growth factor 2
Fibroblasts
Fibroblasts - chemistry
Fibroblasts - classification
Fibroblasts - metabolism
Fibrosis
Gene expression
Gene sequencing
Glycosphingolipids
Growth factors
Heterogeneity
Hormones
Humans
Image resolution
Individualized Instruction
Intermediates
Intracellular signalling
Lipid composition
Lipid metabolism
Lipidomics - methods
Lipids
Mass spectrometry
Mass spectroscopy
Membranes
Metabolic Networks and Pathways
Metabolic pathways
Metabolism
Mode of action
Phenotypes
Signal transduction
Signaling
Skin
Skin - chemistry
Skin - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
Sphingolipids
Sphingolipids - analysis
Sphingolipids - metabolism
Subpopulations
Switches
Transcription
Transcriptome
Transcriptomes
Wound healing
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abh1623