TY - JOUR
T1 - Overexpression of MYB in the Skin Induces Alopecia and Epidermal Hyperplasia
AU - Hu, Yuan
AU - Song, Zhongya
AU - Chen, Jiang
AU - Caulin, Carlos
N1 - Funding Information:
This work was partially supported by the NIH grants R21DE023656 (CC), R01DE026735 (CC), and R01AR061485 (JC); the Adenoid Cystic Carcinoma Research Foundation (CC); and the China Scholarship Council 201706010325 (ZS). Veterinary services and core facilities were supported by the NIH Cancer Center Support Grants P30CA016672 and P30CA023074 . Tissue Acquisition and Cellular/Molecular Analysis facility was supported by the National Cancer Institute Cancer Center Support Grant P30CA023074 .
Publisher Copyright:
© 2019 The Authors
PY - 2020/6
Y1 - 2020/6
N2 - Skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle, and a marked depletion of hair follicle stem cells. Additionally, transgenic mice developed massive epidermal hyperplasia and hyperkeratosis. Global expression profiling not only confirmed that the skin of these mice exhibited transcriptomic features of alopecia and epidermal differentiation, but also revealed features of psoriasis and the inflammatory response. The latter was further confirmed by the increased T-cell infiltration found in the skin of transgenic mice. Overall, these results suggest that tight regulation of MYB expression in the skin is critical to maintain skin homeostasis.
AB - Skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle, and a marked depletion of hair follicle stem cells. Additionally, transgenic mice developed massive epidermal hyperplasia and hyperkeratosis. Global expression profiling not only confirmed that the skin of these mice exhibited transcriptomic features of alopecia and epidermal differentiation, but also revealed features of psoriasis and the inflammatory response. The latter was further confirmed by the increased T-cell infiltration found in the skin of transgenic mice. Overall, these results suggest that tight regulation of MYB expression in the skin is critical to maintain skin homeostasis.
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U2 - 10.1016/j.jid.2019.10.013
DO - 10.1016/j.jid.2019.10.013
M3 - Article
C2 - 31758945
AN - SCOPUS:85076838636
SN - 0022-202X
VL - 140
SP - 1204-1213.e5
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -