期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 36, 页码 22173-22182出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2011310117
关键词
lipids; epidermis; differentiation; keratinocytes; lipidomics
资金
- Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre
- King's College London
- King's College Hospital NHS Foundation Trust
- UK Medical Research Council [G1100073]
- Wellcome Trust [096540/Z/11/Z, 110060/Z/15/Z]
- Unilever
- Wellcome Trust [110060/Z/15/Z, 096540/Z/11/Z] Funding Source: Wellcome Trust
- MRC [MR/R015635/1, G1100073] Funding Source: UKRI
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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