The Jag2/Notch1 signaling axis promotes sebaceous gland differentiation and controls progenitor proliferation.

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  • Additional Information
    • Source:
      Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
    • Subject Terms:
      Receptor, Notch1*/metabolism ; Receptor, Notch1*/genetics ; Cell Differentiation* ; Jagged-2 Protein*/metabolism ; Signal Transduction* ; Cell Proliferation* ; Sebaceous Glands*/metabolism ; Sebaceous Glands*/cytology ; Stem Cells*/metabolism ; Stem Cells*/cytology; Animals ; Mice
    • Abstract:
      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 mouse 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. 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 Interests: SA S.N.F.A. is an employee of Genentech, SC S.C. is an employee of Genentech and holds shares in Roche, KS K.S. is an employee of Genentech and holds shares in Roche, DL D.L. was a Genentech employee, and is currently employed at Roche, and holds shares in Roche, LV L.V. is an employee of Genentech and holds shares in Roche, FP F.P. is an employee of Genentech and holds shares in Roche, CS C.W.S. was a Genentech employee, and holds shares in Roche. C.W.S is currently employed at Gilead Sciences
      (© 2024, Abidi et al.)
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    • Contributed Indexing:
      Keywords: Notch signaling; cell fates; differentiation; mouse; regenerative medicine; stem cells; therapeutic antibodies
    • Accession Number:
      0 (Receptor, Notch1)
      0 (Jagged-2 Protein)
      0 (Notch1 protein, mouse)
      0 (Jag2 protein, mouse)
    • Publication Date:
      Date Created: 20241125 Date Completed: 20241125 Latest Revision: 20241127
    • Publication Date:
      20241202
    • Accession Number:
      PMC11588336
    • Accession Number:
      10.7554/eLife.98747
    • Accession Number:
      39585329