Patop Ines L, Anduaga Ane Martin, Bussi Ivana L, Ceriani M Fernanda, Kadener Sebastian
Biology Department, Brandeis University, Waltham, MA, 02454, USA.
Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir - Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA CONICET), Buenos Aires, Argentina.
bioRxiv. 2023 May 23:2023.05.23.542009. doi: 10.1101/2023.05.23.542009.
Circadian rhythms time physiological and behavioral processes to 24-hour cycles. It is generally assumed that most cells contain self-sustained circadian clocks that drive circadian rhythms in gene expression that ultimately generating circadian rhythms in physiology. While those clocks supposedly act cell autonomously, current work suggests that in some of them can be adjusted by the brain circadian pacemaker through neuropeptides, like the Pigment Dispersing Factor (PDF). Despite these findings and the ample knowledge of the molecular clockwork, it is still unknown how circadian gene expression in is achieved across the body.
Here, we used single-cell and bulk RNAseq data to identify cells within the fly that express core-clock components. Surprisingly, we found that less than a third of the cell types in the fly express core-clock genes. Moreover, we identified Lamina wild field (Lawf) and Ponx-neuro positive (Poxn) neurons as putative new circadian neurons. In addition, we found several cell types that do not express core clock components but are highly enriched for cyclically expressed mRNAs. Strikingly, these cell types express the PDF receptor (), suggesting that PDF drives rhythmic gene expression in many cell types in flies. Other cell types express both core circadian clock components and , suggesting that in these cells, PDF regulates the phase of rhythmic gene expression.
Together, our data suggest three different mechanisms generate cyclic daily gene expression in cells and tissues: canonical endogenous canonical molecular clock, PDF signaling-driven expression, or a combination of both.
昼夜节律将生理和行为过程调整为24小时周期。一般认为,大多数细胞都含有自我维持的生物钟,这些生物钟驱动基因表达中的昼夜节律,最终在生理上产生昼夜节律。虽然这些生物钟据推测是自主发挥作用的,但目前的研究表明,其中一些生物钟可以通过神经肽,如色素分散因子(PDF),由大脑昼夜起搏器进行调节。尽管有这些发现以及对分子生物钟机制的充分了解,但目前仍不清楚全身的昼夜基因表达是如何实现的。
在这里,我们使用单细胞和大量RNA测序数据来识别果蝇体内表达核心生物钟组件的细胞。令人惊讶的是,我们发现果蝇中不到三分之一的细胞类型表达核心生物钟基因。此外,我们将层板野(Lawf)神经元和Ponx神经阳性(Poxn)神经元确定为假定的新昼夜节律神经元。此外,我们发现了几种不表达核心生物钟组件但富含周期性表达mRNA的细胞类型。引人注目的是,这些细胞类型表达PDF受体(),这表明PDF在果蝇的许多细胞类型中驱动节律性基因表达。其他细胞类型同时表达核心昼夜节律生物钟组件和,这表明在这些细胞中,PDF调节节律性基因表达的相位。
总之,我们的数据表明,细胞和组织中每日周期性基因表达是由三种不同机制产生的:典型的内源性典型分子生物钟、PDF信号驱动的表达或两者的组合。