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长期卧床休息期间人类转录组及其昼夜节律组织的广泛动态变化。

Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest.

作者信息

Archer Simon N, Möller-Levet Carla, Bonmatí-Carrión María-Ángeles, Laing Emma E, Dijk Derk-Jan

机构信息

Surrey Sleep Research Centre, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK.

Bioinformatics Core Facility, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK.

出版信息

iScience. 2024 Feb 22;27(3):109331. doi: 10.1016/j.isci.2024.109331. eCollection 2024 Mar 15.

DOI:10.1016/j.isci.2024.109331
PMID:38487016
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10937834/
Abstract

Physiological and molecular processes including the transcriptome change across the 24-h day, driven by molecular circadian clocks and behavioral and systemic factors. It is not known how the temporal organization of the human transcriptome responds to a long-lasting challenge. This may, however, provide insights into adaptation, disease, and recovery. We investigated the human 24-h time series transcriptome in 20 individuals during a 90-day constant bed rest protocol. We show that the protocol affected 91% of the transcriptome with 76% of the transcriptome still affected after 10 days of recovery. Dimensionality-reduction approaches revealed that many affected transcripts were associated with mRNA translation and immune function. The number, amplitude, and phase of rhythmic transcripts, including clock genes, varied significantly across the challenge. These findings of long-lasting changes in the temporal organization of the transcriptome have implications for understanding the mechanisms underlying health consequences of conditions such as microgravity and bed rest.

摘要

包括转录组在内的生理和分子过程在一天24小时内会发生变化,这是由分子生物钟以及行为和全身因素驱动的。目前尚不清楚人类转录组的时间组织如何应对长期挑战。然而,这可能会为适应、疾病和恢复提供见解。我们在一项为期90天的持续卧床休息方案中,对20名个体的人类24小时时间序列转录组进行了研究。我们发现,该方案影响了91%的转录组,在恢复10天后,仍有76%的转录组受到影响。降维方法显示,许多受影响的转录本与mRNA翻译和免疫功能有关。包括时钟基因在内的节律性转录本的数量、振幅和相位在整个挑战过程中都有显著变化。转录组时间组织的这些长期变化的发现,对于理解微重力和卧床休息等情况对健康产生影响的潜在机制具有重要意义。

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