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Damage at the root of cell renewal--UV sensitivity of human epidermal stem cells.

机译:细胞更新的根源受损-人表皮干细胞对紫外线的敏感性。

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BACKGROUND: The epidermis harbors adult stem cells that reside in the basal layer and ensure the continuous maintenance of tissue homeostasis. Various studies imply that stem cells generally possess specific defense mechanisms against several forms of exogenous stress factors. As sun exposition is the most prevalent impact on human skin, this feature would be of particular importance in terms of sensitivity to UV-induced DNA damage. OBJECTIVE: To investigate whether human epidermal stem cells are susceptible to UV-induced DNA damage and subsequent functional impairment. METHODS: A method to isolate human epidermal stem cells from suction blister epidermis was established and validated. Volunteers were treated with solar-simulated irradiation on test areas of the forearm and stem cells were isolated from suction blister material of this region. DNA damage was analyzed by staining for cyclobutane thymidine dimers. The functional consequences of UV-induced damages were assessed by colony forming efficiency assays and gene expression analyses. RESULTS: Compared to an unirradiated control, stem cells isolated from areas that were exposed to solar-simulated radiation showed significantly more DNA lesions. Although the number of stem cells was not reduced by this treatment, a functional impairment of stem cells could be shown by reduced colony forming efficiency and altered gene expression of stem cell markers. CONCLUSIONS: Despite their essential role in skin maintenance, epidermal stem cells are sensitive to physiological doses of UV irradiation in vivo.
机译:背景:表皮具有位于基底层的成体干细胞,可确保组织稳态的持续维持。各种研究表明,干细胞通常具有针对几种形式的外源性应激因素的特异性防御​​机制。由于日晒是对人体皮肤的最普遍影响,因此从对紫外线引起的DNA损伤的敏感性方面来看,此功能特别重要。目的:研究人表皮干细胞是否易受紫外线诱导的DNA损伤和随后的功能损伤。方法:建立并验证了从吸塑水疱表皮中分离人表皮干细胞的方法。在前臂的测试区域对志愿者进行太阳光照射,并从该区域的吸塑材料中分离出干细胞。通过对环丁烷胸苷二聚体染色分析DNA损伤。通过菌落形成效率测定和基因表达分析评估了紫外线引起的损害的功能后果。结果:与未照射的对照组相比,从暴露于太阳模拟辐射的区域分离的干细胞显示出明显更多的DNA损伤。尽管通过这种处理方法并没有减少干细胞的数量,但是可以通过降低菌落形成效率和改变干细胞标记的基因表达来显示干细胞的功能受损。结论:表皮干细胞尽管在皮肤维持中起着重要作用,但对体内紫外线的生理剂量敏感。

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