TY - JOUR
T1 - Through the lens of hair follicle neogenesis, a new focus on mechanisms of skin regeneration after wounding
AU - Wier, Eric M.
AU - Garza, Luis A.
N1 - Funding Information:
The composition of this review was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, part of the National Institutes of Health, under 1F32AR074865-01 to EW and R01AR064297/AR068280 to LAG.
Funding Information:
The composition of this review was supported by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases , part of the National Institutes of Health, under 1F32AR074865-01 to EW and R01AR064297/AR068280 to LAG.
Publisher Copyright:
© 2019
PY - 2020/4
Y1 - 2020/4
N2 - Wound-induced hair follicle neogenesis (WIHN) is a phenomenon that occurs in adult mammalian skin, where fully functional hair follicles are regenerated in the center of large full-thickness excisional wounds. Although originally discovered over 50 years ago in mice and rabbits, within the last decade it has received renewed interest, as the molecular mechanism has begun to be defined. This de novo regeneration of hair follicles largely recapitulates embryonic hair development, requiring canonical Wnt signaling in the epidermis, however, important differences between the two are beginning to come to light. TLR3 mediated double stranded RNA sensing is critical for the regeneration, activating retinoic acid signaling following wounding. Inflammatory cells, including Fgf9-producing γ-δ T cells and macrophages, are also emerging as important mediators of WIHN. Additionally, while dispensable in embryonic hair follicle development, Shh signaling plays a major role in WIHN and may be able to redirect cells fated to scarring wounds into a regenerative phenotype. The cellular basis of WIHN is also becoming clearer, with increasing evidence suggesting an incredible level of cellular plasticity. Multiple stem cell populations, along with lineage switching of differentiated cells all contribute towards the regeneration present in WIHN. Further study of WIHN will uncover key steps in mammalian development and regeneration, potentially leading to new clinical treatments for hair-related disorders or fibrotic scarring.
AB - Wound-induced hair follicle neogenesis (WIHN) is a phenomenon that occurs in adult mammalian skin, where fully functional hair follicles are regenerated in the center of large full-thickness excisional wounds. Although originally discovered over 50 years ago in mice and rabbits, within the last decade it has received renewed interest, as the molecular mechanism has begun to be defined. This de novo regeneration of hair follicles largely recapitulates embryonic hair development, requiring canonical Wnt signaling in the epidermis, however, important differences between the two are beginning to come to light. TLR3 mediated double stranded RNA sensing is critical for the regeneration, activating retinoic acid signaling following wounding. Inflammatory cells, including Fgf9-producing γ-δ T cells and macrophages, are also emerging as important mediators of WIHN. Additionally, while dispensable in embryonic hair follicle development, Shh signaling plays a major role in WIHN and may be able to redirect cells fated to scarring wounds into a regenerative phenotype. The cellular basis of WIHN is also becoming clearer, with increasing evidence suggesting an incredible level of cellular plasticity. Multiple stem cell populations, along with lineage switching of differentiated cells all contribute towards the regeneration present in WIHN. Further study of WIHN will uncover key steps in mammalian development and regeneration, potentially leading to new clinical treatments for hair-related disorders or fibrotic scarring.
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U2 - 10.1016/j.semcdb.2019.10.002
DO - 10.1016/j.semcdb.2019.10.002
M3 - Review article
C2 - 31607627
AN - SCOPUS:85073009360
SN - 1084-9521
VL - 100
SP - 122
EP - 129
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
ER -