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J Invest Dermatol. 2018 Mar;138(3):511-519. doi: 10.1016/j.jid.2017.09.047. Epub 2017 Oct 26.

Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ: Lessons from Lichen Planopilaris.

Author information

1
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research Biomedical Research Centre, Manchester, UK; Department of Dermatology, Osaka City University Graduate School of Medicine, Japan.
2
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research Biomedical Research Centre, Manchester, UK.
3
Monasterium Laboratory, Münster, Germany.
4
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research Biomedical Research Centre, Manchester, UK; Dermatology Centre, University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK.
5
Monasterium Laboratory, Münster, Germany; Department of Dermatology, University of Münster, Münster, Germany.
6
Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria.
7
Departments of Immunology and Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
8
Department of Pathology, University General Hospital of Murcia, Murcia, Spain.
9
Mediteknia Dermatology Clinic, Medical Pathology Group, Instituto de Investigación Biosanitaria, Universidad de Las Palmas de Gran Canaria, Gran Canaria, Canary Islands, Spain.
10
Department of Zoology, University of Kerala, India.
11
School of Dentistry, University of Manchester, Manchester, UK.
12
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre, National Institute for Health Research Biomedical Research Centre, Manchester, UK. Electronic address: ralf.paus@manchester.ac.uk.

Abstract

Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator-activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator-activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator-activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris.

PMID:
29106928
DOI:
10.1016/j.jid.2017.09.047

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