Table2_Chronic sleep loss disrupts rhythmic gene expression in Drosophila.xlsx

Genome-wide profiling of rhythmic gene expression has offered new avenues for studying the contribution of circadian clock to diverse biological processes. Sleep has been considered one of the most important physiological processes that are regulated by the circadian clock, however, the effects of chronic sleep loss on rhythmic gene expression remain poorly understood. In the present study, we exploited Drosophila sleep mutants insomniac1 (inc1) and wide awakeD2 (wakeD2) as models for chronic sleep loss. We profiled the transcriptomes of head tissues collected from 4-week-old wild type flies, inc1 and wakeD2 at timepoints around the clock. Analysis of gene oscillation revealed a substantial loss of rhythmicity in inc1 and wakeD2 compared to wild type flies, with most of the affected genes common to both mutants. The disruption of gene oscillation was not due to changes in average gene expression levels. We also identified a subset of genes whose loss of rhythmicity was shared among animals with chronic sleep loss and old flies, suggesting a contribution of aging to chronic, sleep-loss-induced disruption of gene oscillation.

节律性基因表达的全基因组分析，为探究昼夜节律时钟（circadian clock）对多种生物学过程的调控贡献开辟了全新途径。睡眠被视作受昼夜节律时钟调控的核心生理过程之一，但目前学界对慢性睡眠缺失对节律性基因表达的影响仍缺乏深入认知。本研究以果蝇睡眠突变体insomniac1（inc1）与wide awakeD2（wakeD2）作为慢性睡眠缺失的研究模型。我们于24小时内的多个时间点，分别采集4周龄野生型果蝇、inc1突变体果蝇与wakeD2突变体果蝇的头部组织，并对其转录组进行了分析。针对基因振荡（gene oscillation）的分析结果显示，相较于野生型果蝇，inc1与wakeD2突变体的基因节律性出现显著丧失，且二者受影响的基因大多存在重叠。此类基因振荡紊乱并非由基因平均表达水平的变化所导致。我们还鉴定出一类基因，其节律性丧失在慢性睡眠缺失果蝇与老年果蝇中均存在，这提示衰老参与了慢性睡眠缺失诱导的基因振荡紊乱过程。