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    Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris

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    Publication date
    2018-03-01
    Author
    Imanishi, H.
    Answell, David M.
    Chéret, J.
    Harries, M.
    Bertolini, M.
    Sepp, N.
    Biro, T.
    Poblet, E.
    Jimenez, F.
    Hardman, J.
    Panicker, S.P.
    Ward, C.M.
    Paus, R.
    Show allShow less
    Keyword
    AGED
    N-Acetyl-GED
    EMT
    eSC
    Rights
    (c) 2018 The Authors.
    Peer-Reviewed
    Yes
    
    Metadata
    Show full item record
    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.
    URI
    http://hdl.handle.net/10454/17809
    Version
    Accepted manuscript
    Citation
    Imanishi H, Ansell DM, Chéret J et al (2018) Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris. Journal of Investigative Dermatology. 138(3): 511-519.
    Link to publisher’s version
    https://doi.org/10.1016/j.jid.2017.09.047
    Type
    Article
    Collections
    Life Sciences Publications

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