Human epidermal stem cell differentiation is modulated by specific lipid subspecies.
| Autor: | Vietri Rudan M; Centre for Stem Cells and Regenerative Medicine, King's College London, SE1 9RT London, United Kingdom., Mishra A; Centre for Stem Cells and Regenerative Medicine, King's College London, SE1 9RT London, United Kingdom.; European Bioinformatics Institute, CB10 1SD Hinxton, United Kingdom., Klose C; Lipotype GmbH, 01307 Dresden, Germany., Eggert US; Randall Centre for Cell and Molecular Biophysics, King's College London, SE1 1UL London, United Kingdom., Watt FM; Centre for Stem Cells and Regenerative Medicine, King's College London, SE1 9RT London, United Kingdom; fiona.watt@kcl.ac.uk. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Sep 08; Vol. 117 (36), pp. 22173-22182. Date of Electronic Publication: 2020 Aug 25. |
| DOI: | 10.1073/pnas.2011310117 |
| Abstrakt: | 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. Competing Interests: Competing interest statement: C.K. is the head of research and development at Lipotype GmbH. (Copyright © 2020 the Author(s). Published by PNAS.) |
| Databáze: | MEDLINE |
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