Epithelial-to-mesenchymal stem cell transition in a human organ: Lessons from Lichen Planopilaris
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2018-03-01Author
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.
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(c) 2018 The Authors.Peer-Reviewed
Yes
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Show full item recordAbstract
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.Version
Accepted manuscriptCitation
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 Version of Record
https://doi.org/10.1016/j.jid.2017.09.047Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.jid.2017.09.047