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

Hisayoshi Imanishi, David M. Ansell, Jérémy Chéret, Matthew Harries, Marta Bertolini, Norbert Sepp, Tamás Bíró, Enrique Poblet, Francisco Jimenez, Jonathan Hardman, Sreejith Parameswara Panicker, Christopher M. Ward, Ralf Paus

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)511-519
Number of pages9
JournalJournal of Investigative Dermatology
Volume138
Issue number3
DOIs
StatePublished - Mar 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Imanishi, H., Ansell, D. M., Chéret, J., Harries, M., Bertolini, M., Sepp, N., Bíró, T., Poblet, E., Jimenez, F., Hardman, J., Panicker, S. P., Ward, C. M., & Paus, R. (2018). Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ: Lessons from Lichen Planopilaris. Journal of Investigative Dermatology, 138(3), 511-519. https://doi.org/10.1016/j.jid.2017.09.047