Single-cell RNA sequencing of human epidermis identifies Lunatic fringe as a novel regulator of the stem cell compartment

人类表皮的单细胞 RNA 测序表明疯子边缘是干细胞区室的新调节器

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作者:Victor Augusti Negri, Blaise Louis, Sebastiaan Zijl, Clarisse Ganier, Christina Philippeos, Shahnawaz Ali, Gary Reynolds, Muzlifah Haniffa, Fiona M Watt

Abstract

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.

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