King's College London

Research portal

Human epidermal stem cell differentiation is modulated by specific lipid subspecies

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)22173-22182
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number36
Early online date25 Aug 2020
DOIs
E-pub ahead of print25 Aug 2020
Published8 Sep 2020

Bibliographical note

Copyright © 2020 the Author(s). Published by PNAS.

King's Authors

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.

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454