Document Type

Article

Publication Date

11-25-2023

Comments

This article is the author's final published version in iScience, Volume 26, Issue 12, December 2023, Article number 108568.

The published version is available at https://doi.org/10.1016/j.isci.2023.108568.

Copyright © 2023 The Author(s).

Abstract

Stem cells (SCs) are critical to maintain tissue homeostasis. However, it is currently not known whether signaling through cell junctions protects quiescent epithelial SC reservoirs from depletion during disease-inflicted damage. Using the autoimmune model disease pemphigus vulgaris (PV), this study reveals an unprecedented role for a desmosomal cadherin in governing SC quiescence and regeneration through adhesion signaling in the multipotent mouse hair follicle compartment known as the bulge. Autoantibody-mediated, mechanical uncoupling of desmoglein (Dsg) 3 transadhesion activates quiescent bulge SC which lose their multipotency and stemness, become actively cycling, and finally delaminate from their epithelial niche. This then initiates a self-organized regenerative program which restores Dsg3 function and bulge morphology including SC quiescence and multipotency. These profound changes are triggered by the sole loss of functional Dsg3, resemble major signaling events in Dsg3−/− mice, and are driven by SC-relevant EGFR activation and Wnt modulation requiring longitudinal repression of Hedgehog signaling.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Additional Files
Document S1. Figures S1–S6.pdf (3157 kB)

PubMed ID

38162019

Language

English

Download

Included in

Dermatology Commons

Share

COinS