RT Journal Article
SR Electronic
T1 The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.05.05.592588
DO 10.1101/2024.05.05.592588
A1 Abidi, Syeda Nayab Fatima
A1 Chan, Sara
A1 Seidel, Kerstin
A1 Lafkas, Daniel
A1 Vermeulen, Louis
A1 Peale, Frank
A1 Siebel, Christian W.
YR 2024
UL http://biorxiv.org/content/early/2024/05/09/2024.05.05.592588.abstract
AB The sebaceous gland (SG) is a vital appendage of the epidermis, and its normal homeostasis and function is crucial for effective maintenance of the skin barrier. Notch signaling is a well-known regulator of epidermal differentiation, and has also been shown to be involved in postnatal maintenance of SGs. However, the precise role of Notch signaling in regulating SG differentiation in the adult homeostatic skin remains unclear. While there is evidence to suggest that Notch1 is the primary Notch receptor involved in regulating the differentiation process, the ligand remains unknown. Using monoclonal therapeutic antibodies designed to specifically inhibit of each of the Notch ligands or receptors, we have identified the Jag2/Notch1 signaling axis as the primary regulator of sebocyte differentiation in homeostatic skin. Mature sebocytes are lost upon specific inhibition of the Jag2 ligand or Notch1 receptor, resulting in the accumulation of proliferative stem/progenitor cells in the SG. Most strikingly, this phenotype is reversible, as these stem/progenitor cells re-enter differentiation when the inhibition of Notch activity is lifted. Thus, Notch activity promotes correct sebocyte differentiation, and is required to restrict progenitor proliferation.Competing Interest StatementThe authors have declared no competing interest.