Differential Phasing between Circadian Clocks in the Brain and Peripheral Organs in Humans
Differential Phasing between Circadian Clocks in the Brain and Peripheral Organs in Humans
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DOI：
10.1177/0748730416668049
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发表时间：
2016-12-01
影响因子：
3.5
通讯作者：
Butte, Atul J.
中科院分区：
文献类型：
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作者：
Hughey, Jacob J.;Butte, Atul J.
哺乳动物生理学的每日定时是由整个身体的生物钟协调的。尽管对生物钟基因表达的测量表明，小鼠体内的生物钟通常是同步的，但人类的情况仍不清楚。我们使用了来自五项研究的公开数据，包括超过1000个样本，以比较人脑和人类血液中昼夜节律基因表达的相位。令人惊讶的是，在控制年龄后，大脑中的时钟基因表达相对于血液中的时钟基因表达延迟了8.5小时。然后，我们研究了时钟基因表达在两个额外的人类器官和其他九种哺乳动物的器官，以及在视交叉上核（SCN）。在SCN以外的大多数组织中，时钟基因直系同源物的表达在昼夜物种之间显示出类似于12小时的相位差。这种模式的例外是人类大脑，其相位类似于SCN。我们的研究结果突出了多组织，多物种荟萃分析的价值，并对我们理解人类昼夜节律系统产生影响。
The daily timing of mammalian physiology is coordinated by circadian clocks throughout the body. Although measurements of clock gene expression indicate that these clocks in mice are normally in phase with each other, the situation in humans remains unclear. We used publicly available data from five studies, comprising over 1000 samples, to compare the phasing of circadian gene expression in human brain and human blood. Surprisingly, after controlling for age, clock gene expression in brain was phase-delayed by similar to 8.5 h relative to that of blood. We then examined clock gene expression in two additional human organs and in organs from nine other mammalian species, as well as in the suprachiasmatic nucleus (SCN). In most tissues outside the SCN, the expression of clock gene orthologs showed a phase difference of similar to 12 h between diurnal and nocturnal species. The exception to this pattern was human brain, whose phasing resembled that of the SCN. Our results highlight the value of a multi-tissue, multi-species meta-analysis, and have implications for our understanding of the human circadian system.