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压力相关的黑素细胞干细胞和 ORS 无色素黑素细胞在体外人毛囊模型中的异位分化。

Stress-associated ectopic differentiation of melanocyte stem cells and ORS amelanotic melanocytes in an ex vivo human hair follicle model.

机构信息

Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute, Cambridge, MA, USA.

出版信息

Exp Dermatol. 2021 Apr;30(4):578-587. doi: 10.1111/exd.14309. Epub 2021 Mar 3.

DOI:10.1111/exd.14309
PMID:33598985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8600567/
Abstract

Hair greying depends on the altered presence and functionality of hair follicle melanocytes. Melanocyte stem cells (MelSCs) reside in the bulge of hair follicles and give rise to migrating and differentiating progeny during the anagen phase. Ageing, genotoxic stress, redox stress and multiple behaviour-associated acute stressors have been seen to induce hair greying by depleting the MelSC pool, a phenomenon which is accompanied by ectopic pigmentation of these cells, followed by their depletion from the stem cell niche. This aberrant differentiation produces a state from which a return to stem cell-like quiescence appears to be lost. The cellular features of stress-induced hair greying have been extensively studied in murine models. Here, we describe a method to assess and quantify human hair follicle MelSC differentiation by measuring ectopically pigmented MelSCs in isolated human hair follicles exposed to specific stress signal mediators. Ionizing radiation, hydrogen peroxide and noradrenaline have been shown to cause hair greying in mice. We demonstrate here that isolated, ex vivo cultured human hair follicles exposed to these treatments display similar ectopic pigmentation within the bulge area which is accompanied by induction of differentiated melanocytic markers. This study suggests that as in murine models, stress signalling induces closely matching phenotypic changes in human hair follicles which can be monitored and studied as a surrogate model for early steps in human hair greying.

摘要

头发变白取决于毛囊黑素细胞的存在和功能改变。黑素细胞干细胞(MelSCs)存在于毛囊的隆起处,在生长期会产生迁移和分化的后代。衰老、遗传毒性应激、氧化应激和多种与行为相关的急性应激源已被发现通过耗尽 MelSC 池来诱导头发变白,这一现象伴随着这些细胞的异位色素沉着,随后它们从干细胞龛中耗尽。这种异常分化产生了一种状态,似乎失去了恢复到干细胞样静止状态的能力。在小鼠模型中,已经对应激诱导的头发变白的细胞特征进行了广泛研究。在这里,我们描述了一种通过测量暴露于特定应激信号介质的分离人毛囊中的异位色素化 MelSCs 来评估和量化人毛囊 MelSC 分化的方法。电离辐射、过氧化氢和去甲肾上腺素已被证明可导致小鼠头发变白。我们在这里证明,暴露于这些处理的分离的、离体培养的人毛囊在隆起区域显示出类似的异位色素沉着,同时伴随着分化的黑色素细胞标记物的诱导。这项研究表明,与在小鼠模型中一样,应激信号在人类毛囊中诱导出相似的表型变化,可以作为人类头发变白早期步骤的替代模型进行监测和研究。

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本文引用的文献

1
Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp.人类灰白头发毛囊中的应激感应:易白发头皮中毛球黑素细胞中的共济失调毛细血管扩张突变基因(ATM)耗竭。
Sci Rep. 2020 Oct 30;10(1):18711. doi: 10.1038/s41598-020-75334-9.
2
The biology of human hair greying.人类头发变白的生物学。
Biol Rev Camb Philos Soc. 2021 Feb;96(1):107-128. doi: 10.1111/brv.12648. Epub 2020 Sep 23.
3
Medication-Induced Repigmentation of Gray Hair: A Systematic Review.药物诱导白发复色:一项系统评价
Skin Appendage Disord. 2020 Jan;6(1):1-10. doi: 10.1159/000504414. Epub 2019 Dec 17.
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Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells.交感神经的过度激活导致黑素细胞干细胞耗竭。
Nature. 2020 Jan;577(7792):676-681. doi: 10.1038/s41586-020-1935-3. Epub 2020 Jan 22.
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Effects of the selective TrkA agonist gambogic amide on pigmentation and growth of human hair follicles in vitro.选择性 TrkA 激动剂藤黄酰胺对体外培养的人毛囊色素形成和生长的影响。
PLoS One. 2019 Aug 29;14(8):e0221757. doi: 10.1371/journal.pone.0221757. eCollection 2019.
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Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials.皮肤及其附属物色素沉着中的黑素细胞干细胞调控:生物学模式与治疗潜能。
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