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A desmosomal cadherin controls multipotent hair follicle stem cell quiescence and orchestrates regeneration through adhesion signaling

Authors :
William V.J. Hariton
Katja Schulze
Siavash Rahimi
Taravat Shojaeian
Laurence Feldmeyer
Roman Schwob
Andrew M. Overmiller
Beyza S. Sayar
Luca Borradori
Mỹ G. Mahoney
Arnaud Galichet
Eliane J. Müller
Source :
iScience, Vol 26, Iss 12, Pp 108568- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Summary: 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.

Details

Language :
English
ISSN :
25890042
Volume :
26
Issue :
12
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.f8c4ec496e3c410ab9492b5aed9727df
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2023.108568