The period length of fibroblast circadian gene expression varies widely among human individuals.
The period length of fibroblast circadian gene expression varies widely among human individuals.
复制标题
成纤维细胞昼夜节律基因表达的周期长度在人的个体中差异很大。
DOI：
10.1371/journal.pbio.0030338
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发表时间：
2005-10
期刊：
影响因子：
9.8
通讯作者：
Schibler U
中科院分区：
文献类型：
--
作者：
Brown SA;Fleury-Olela F;Nagoshi E;Hauser C;Juge C;Meier CA;Chicheportiche R;Dayer JM;Albrecht U;Schibler U
哺乳动物的昼夜节律行为是由大脑下丘脑视交叉上核的中央时钟控制的，其内在周期长度被认为影响日常活动的相位。测量这个周期的长度，通常通过长时间的观察来完成，对人类来说是困难和昂贵的。由于与视交叉上核相似的生物钟存在于大多数细胞类型中，我们能够设计一种慢病毒生物钟报告基因，该基因允许在单个皮肤活检中表征生物钟。利用它，我们已经确定了19个人类个体的周期长度。所有受试者的平均值（24.5小时）与在不存在光输入和睡眠-觉醒周期反馈的混杂效应的情况下评估昼夜节律周期的研究中获得的人类昼夜节律生理学的平均值密切匹配。然而，从不同个体的活检测量的周期长度的分布比报道的昼夜生理学更广泛。在含有昼夜节律基因破坏的小鼠品系中，当比较车轮运行行为与成纤维细胞周期长度时，观察到类似的趋势。在小鼠中，成纤维细胞周期长度的个体间差异与转轮活动的周期相关;在人类中，来自不同个体的成纤维细胞表现出广泛的昼夜节律周期。鉴于其鲁棒性，所提出的程序应允许人类时期长度的数量性状映射。一种新的方法允许使用单个皮肤活检来表征人类和小鼠的昼夜节律。
Mammalian circadian behavior is governed by a central clock in the suprachiasmatic nucleus of the brain hypothalamus, and its intrinsic period length is believed to affect the phase of daily activities. Measurement of this period length, normally accomplished by prolonged subject observation, is difficult and costly in humans. Because a circadian clock similar to that of the suprachiasmatic nucleus is present in most cell types, we were able to engineer a lentiviral circadian reporter that permits characterization of circadian rhythms in single skin biopsies. Using it, we have determined the period lengths of 19 human individuals. The average value from all subjects, 24.5 h, closely matches average values for human circadian physiology obtained in studies in which circadian period was assessed in the absence of the confounding effects of light input and sleep–wake cycle feedback. Nevertheless, the distribution of period lengths measured from biopsies from different individuals was wider than those reported for circadian physiology. A similar trend was observed when comparing wheel-running behavior with fibroblast period length in mouse strains containing circadian gene disruptions. In mice, inter-individual differences in fibroblast period length correlated with the period of running-wheel activity; in humans, fibroblasts from different individuals showed widely variant circadian periods. Given its robustness, the presented procedure should permit quantitative trait mapping of human period length. A novel method permits characterization of circadian rhythms in humans and mice using single skin biopsies.
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