Single-cell RNA sequencing of human epidermis identifies Lunatic fringe as a novel regulator of the stem cell compartment
Single-cell RNA sequencing (scRNA-seq) of human skin provides a tool for validating observations from in vitro experimental models. By analyzing a published dataset of healthy adult epidermis, we confirm that the basal epidermal layer is heterogeneous, and three subpopulations of non-dividing cells...
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Veröffentlicht in: | Stem cell reports 2023-11, Vol.18 (11), p.2047-2055 |
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Zusammenfassung: | Single-cell RNA sequencing (scRNA-seq) of human skin provides a tool for validating observations from in vitro experimental models. By analyzing a published dataset of healthy adult epidermis, we confirm that the basal epidermal layer is heterogeneous, and three subpopulations of non-dividing cells can be distinguished. We show that Delta-like ligand 1 (DLL1) is expressed in a subset of basal cells previously identified as stem cells in cultured human keratinocytes and map the distribution of other Notch ligands and receptors to specific epidermal cell compartments. Although DLL1 is expressed at low levels, it is expressed in the same cell state as the Notch regulator, Lunatic -fringe (LFNG, O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase). Overexpression of LFNG amplifies the effects of DLL1 in cultured keratinocytes, increasing proliferation and colony-forming ability. We conclude that using scRNA-seq resources from healthy human skin not only validates previous experimental data but allows formulation of testable new hypotheses.
•The basal compartment of human epidermis is heterogeneous•Notch signaling plays a role in stem cell maintenance and differentiation•LFNG amplifies DLL1 signaling in stem cells
In this study, Negri and colleagues re-analyze published single-cell RNA sequencing data from adult human epidermis to validate previous conclusions from cultured keratinocytes and to generate new mechanistic hypotheses. They show that the basal layer is heterogeneous, and co-expression of DLL1 and LFNG in stem cells amplifies the effect of DLL1 in stem cell maintenance. |
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ISSN: | 2213-6711 2213-6711 |
DOI: | 10.1016/j.stemcr.2023.09.007 |