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1.
Cell Rep ; 43(7): 114347, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38941190

RESUMO

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.

2.
bioRxiv ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38712094

RESUMO

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing Il17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.

3.
Exp Dermatol ; 30(4): 472-478, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33025661

RESUMO

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E-cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Queratinas/metabolismo , Glândulas Sebáceas/metabolismo , Fenômenos Fisiológicos da Pele , Animais , Camundongos , Camundongos Endogâmicos C57BL
4.
Cell Rep ; 19(4): 809-821, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28445731

RESUMO

During development and regeneration, matrix progenitors undergo terminal differentiation to form the concentric layers of the hair follicle. These differentiation events are thought to require signals from the mesenchymal dermal papilla (DP); however, it remains unclear how DP-progenitor cell interactions govern specific cell fate decisions. Here, we show that the hair follicle differentiated layers are specified asynchronously, with early matrix progenitors initiating differentiation before surrounding the DP. Furthermore, these early matrix cells can undergo terminal differentiation in the absence of Shh, BMP signaling, and DP maturation. Whereas early matrix progenitors form the hair follicle companion layer, later matrix populations progressively form the inner root sheath and hair shaft. Altogether, our findings characterize some of the earliest terminal differentiation events in the hair follicle and reveal that the matrix progenitor pool can be divided into early and late phases based on distinct temporal, molecular, and functional characteristics.


Assuntos
Diferenciação Celular/fisiologia , Folículo Piloso/citologia , Células-Tronco Mesenquimais/citologia , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Derme/citologia , Fator de Transcrição GATA3/metabolismo , Folículo Piloso/metabolismo , Proteínas Hedgehog/deficiência , Proteínas Hedgehog/genética , Queratina-6/metabolismo , Queratinas/genética , Queratinas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
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