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

Hariton, William V J; Schulze, Katja; Rahimi, Siavash; Shojaeian, Taravat; Feldmeyer, Laurence; Schwob, Roman; Overmiller, Andrew M; Sayar, Beyza; Borradori, Luca; Mahoney, Mỹ G; Galichet, Arnaud; Müller, Eliane Jasmine (2023). A desmosomal cadherin controls multipotent hair follicle stem cell quiescence and orchestrates regeneration through adhesion signaling. iScience, 26(12), p. 108568. Elsevier 10.1016/j.isci.2023.108568

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pathologie > Forschungsgruppe Dermatologie

UniBE Contributor:

Hariton, William Vincent, Schulze, Katja, Rahimi, Siavash, Shojaeian, Taravat, Feldmeyer, Laurence, Schwob, Roman Alexander, Sayar, Beyza, Borradori, Luca, Galichet, Arnaud, Müller, Eliane Jasmine

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2589-0042

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

03 Jan 2024 15:40

Last Modified:

21 Jun 2024 09:58

Publisher DOI:

10.1016/j.isci.2023.108568

PubMed ID:

38162019

Uncontrolled Keywords:

Cell biology Molecular biology

BORIS DOI:

10.48350/191069

URI:

https://boris.unibe.ch/id/eprint/191069

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