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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

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

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. 06 May 2020 (has links)
Yes / 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.

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