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

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

iScience (Dec 2023)

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

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

Affiliations

William V.J. Hariton: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
Katja Schulze: DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
Siavash Rahimi: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland
Taravat Shojaeian: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland
Laurence Feldmeyer: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Roman Schwob: DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
Andrew M. Overmiller: Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Beyza S. Sayar: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland
Luca Borradori: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland
Mỹ G. Mahoney: Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Arnaud Galichet: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
Eliane J. Müller: Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; Department for BioMedical Research, Molecular Dermatology and Stem Cell Research, University of Bern, 3008 Bern, Switzerland; DermFocus, Vetsuisse Faculty, University of Bern, 3008 Bern, Switzerland; Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland; Corresponding author

Journal volume & issue: Vol. 26, no. 12
p. 108568

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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