Epithelial-mesenchymal stem cell transition in a human organ: Lessons from lichen planopilaris

Hisayoshi Imanishi, David Ansell, J Chéret, Matthew Harries, M Bertolini, N Sepp, T Bíró, E Poblet, F Jimenez, Jonathan Hardman, S Parameswara Panicker, Christopher Ward, Ralf Paus

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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 (HFs), during the inflammatory permanent alopecia, lichen planopilaris (LPP). We show for the first time that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with TGF-ß1, EGF, and interferon-γ administration. Moreover, induction of EMT within primary human eSCs can be
prevented and even partially reversed ex vivo by PPAR-γ agonists, likely through suppression of TGFβ signaling pathway. Furthermore, we show that PPAR-γ agonism also attenuates the EMT signature even in lesional LPP HFs ex vivo.
Thus, we introduce LPP as a model disease for pathological EMT in human adult eSCs, report the first preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ and show that PPAR-γ agonists are promising agents for suppressing and partially reversing EMT in human HF eSCs ex vivo, including in LLP.
Original languageEnglish
JournalJournal of Investigative Dermatology
Early online date26 Oct 2017
DOIs
Publication statusPublished - 2017

Research Beacons, Institutes and Platforms

  • Manchester Institute for Collaborative Research on Ageing

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