國家衛生研究院 NHRI:Item 3990099045/12665
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    题名: Gasdermin A3-mediated cell death causes niche collapse and precocious activation of hair follicle stem cells
    作者: Li, ST;Suen, WJ;Kao, CH;Yang, MK;Yang, LT
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Hair follicles undergo recurrent growth, regression, and resting phases throughout postnatal life, which is supported by hair follicle stem cells (HFSCs). The niche components of HFSCs are important to maintain their quiescence and stemness. Gasdermin A3 (Gsdma3) gain-of-function mutations in mice cause chronic skin inflammation, aberrant hair cycle, and progressive hair loss, reminiscent of scarring alopecia in humans. However, the mechanism underlying these defects remains elusive. Here, we used a combined Cre/loxP and rtTA/TRE system to study the spatiotemporal effect of Gsdma3 overexpression on distinct hair cycle stages. We found that Gsdma3-mediated cell death affects anagen initiation, anagen progression, and catagen-telogen transition. Induced Gsdma3 expression causes bulge inner layer (BIL) collapse and precocious HFSC activation, leading to subsequent HF degeneration. Although macrophages and dendritic cells are recruited to the bulge region, in vivo depletion of these cells using a neutralizing antibody does not alleviate cell death in the bulge/hair germ, indicating that macrophages are less likely to cause immediate HF deletion. Our data suggest that dysregulated Gsdma3 causes BIL necrosis to induce club hair shedding and immediate anagen re-entry without going through telogen morphology, which implicates a role for Gsdma3 in HFSC niche maintenance.
    日期: 2020-11
    關聯: Journal of Investigative Dermatology. 2020 Nov;140(11):2117-2128.
    Link to: http://dx.doi.org/10.1016/j.jid.2020.02.033
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000581092200012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85085342096
    显示于类别:[楊良棟] 期刊論文

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