期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-47232-2
关键词
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资金
- UK Medical Research Council [MR/PO18823/1]
- Biotechnology and Biological Sciences Research Council [BB/M007219/1]
- Wellcome Trust [206439/Z/17/Z]
- EU Marie Curie Fellowship
- National Council for Scientific and Technological Development-Brazil (CNPq)
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award
- King's College London
- King's College Hospital NHS Foundation Trust
- BBSRC [BB/M007219/1] Funding Source: UKRI
- Wellcome Trust [206439/Z/17/Z] Funding Source: Wellcome Trust
Epidermal homeostasis depends on a balance between self-renewal of stem cells and terminal differentiation of their progeny. Notch signalling is known to play a role in epidermal stem cell patterning and differentiation. However, the molecular mechanisms are incompletely understood. Here we demonstrate dynamic patterns of Notch ligand and receptor expression in cultured human epidermis. Notch2 and 3 act together to promote differentiation, while Notch1 decreases stem cell proliferation. The Notch ligand Jagged1 triggers differentiation when presented on an adhesive substrate or on polystyrene beads and over-rides the differentiation inhibitory effect of cell spreading. In contrast, Delta-like 1 (Dll1) overexpression abrogates the pro-differentiation effect of Jagged1 in a cell autonomous fashion. We conclude that Dll1 expression by stem cells not only stimulates differentiation of neighbouring cells in trans, but also inhibits differentiation cell autonomously. These results highlight the distinct roles of different Notch receptors and ligands in controlling epidermal homeostasis.
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