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Human epidermal stem cell differentiation is modulated by specific lipid subspecies

Authors
  • Vietri Rudan, Matteo1
  • Mishra, Ajay1, 2
  • Klose, Christian3
  • Eggert, Ulrike S.1
  • Watt, Fiona M.1
  • 1 King’s College London, United Kingdom , (United Kingdom)
  • 2 European Bioinformatics Institute, United Kingdom , (United Kingdom)
  • 3 Lipotype GmbH, Germany , (Germany)
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Aug 25, 2020
Volume
117
Issue
36
Pages
22173–22182
Identifiers
DOI: 10.1073/pnas.2011310117
PMID: 32843345
PMCID: PMC7486749
Source
PubMed Central
Keywords
License
Green

Abstract

While the lipids of the outer layers of mammalian epidermis and their contribution to barrier formation have been extensively described, the role of individual lipid species in the onset of keratinocyte differentiation remains unknown. A lipidomic analysis of primary human keratinocytes revealed accumulation of numerous lipid species during suspension-induced differentiation. A small interfering RNA screen of 258 lipid-modifying enzymes identified two genes that on knockdown induced epidermal differentiation: ELOVL1 , encoding elongation of very long-chain fatty acids protein 1, and SLC27A1 , encoding fatty acid transport protein 1. By intersecting lipidomic datasets from suspension-induced differentiation and knockdown keratinocytes, we pinpointed candidate bioactive lipid subspecies as differentiation regulators. Several of these—ceramides and glucosylceramides—induced differentiation when added to primary keratinocytes in culture. Our results reveal the potential of lipid subspecies to regulate exit from the epidermal stem cell compartment.

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