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 language | English (US) |
|---|---|
| Pages (from-to) | 511-519 |
| Number of pages | 9 |
| Journal | Journal of Investigative Dermatology |
| Volume | 138 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2018 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology
Cite this
Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ : Lessons from Lichen Planopilaris. / Imanishi, Hisayoshi; Ansell, David M.; Chéret, Jérémy; Harries, Matthew; Bertolini, Marta; Sepp, Norbert; Bíró, Tamás; Poblet, Enrique; Jimenez, Francisco; Hardman, Jonathan; Panicker, Sreejith Parameswara; Ward, Christopher M.; Paus, Ralf.
In: Journal of Investigative Dermatology, Vol. 138, No. 3, 01.03.2018, p. 511-519.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epithelial-to-Mesenchymal Stem Cell Transition in a Human Organ
T2 - Lessons from Lichen Planopilaris
AU - Imanishi, Hisayoshi
AU - Ansell, David M.
AU - Chéret, Jérémy
AU - Harries, Matthew
AU - Bertolini, Marta
AU - Sepp, Norbert
AU - Bíró, Tamás
AU - Poblet, Enrique
AU - Jimenez, Francisco
AU - Hardman, Jonathan
AU - Panicker, Sreejith Parameswara
AU - Ward, Christopher M.
AU - Paus, Ralf
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042513889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042513889&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2017.09.047
DO - 10.1016/j.jid.2017.09.047
M3 - Article
C2 - 29106928
AN - SCOPUS:85042513889
VL - 138
SP - 511
EP - 519
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 3
ER -