Large-scale analysis reveals spatiotemporal circadian patterns of cilia transcriptomes in the primate brain
Large-scale analysis reveals spatiotemporal circadian patterns of cilia transcriptomes in the primate brain
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DOI：
10.1002/jnr.24919
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发表时间：
2021-07-26
影响因子：
4.2
通讯作者：
Alachkar, Amal
中科院分区：
文献类型：
--
作者：
Baldi, Pierre;Alhassen, Wedad;Alachkar, Amal
纤毛是动态的亚细胞系统，其核心结构和功能组件以高度协调的方式运行。由于纤毛感受到的许多环境刺激本质上是昼夜节律的，因此有理由推测编码纤毛结构和功能成分的基因遵循节律的昼夜表达模式。利用计算方法和灵长类动物最大的时空基因表达图谱，我们识别和分析了22个灵长类脑区纤毛基因的昼夜节律表达。我们发现，大约73%的纤毛转录产物至少在22个大脑区域中的一个区域表现出昼夜节律。与转录组的其余部分相比，在12个大脑区域中，纤毛转录本明显富含昼夜节律振荡转录本。纤毛昼夜节律转录本的时相偏离了大多数背景昼夜节律转录本的时相，编码纤毛体基成分的转录本占纤毛昼夜节律转录本的大部分。此外，相邻或功能相连的脑核与昼夜节律纤毛基因有很大的重叠互补。最值得注意的是，纤毛昼夜节律转录本在这些结构中以顺序的方式达到顶峰，这与与运动协调有关的基底节-皮质回路的激活顺序相似，尽管是在完全不同的时间尺度上。这些发现支持纤毛基因表达的昼夜节律时空协调在基底节-皮质回路和运动控制的正常生理中的作用。研究基底神经节-皮质环路和其他大脑环路中有组织的纤毛节律性可能有助于开发更好的功能模型，并有助于阐明纤毛功能对这些环路以及运动和其他行为调节的因果影响。
Cilia are dynamic subcellular systems, with core structural and functional components operating in a highly coordinated manner. Since many environmental stimuli sensed by cilia are circadian in nature, it is reasonable to speculate that genes encoding cilia structural and functional components follow rhythmic circadian patterns of expression. Using computational methods and the largest spatiotemporal gene expression atlas of primates, we identified and analyzed the circadian rhythmic expression of cilia genes across 22 primate brain areas. We found that around 73% of cilia transcripts exhibited circadian rhythmicity across at least one of 22 brain regions. In 12 brain regions, cilia transcriptomes were significantly enriched with circadian oscillating transcripts, as compared to the rest of the transcriptome. The phase of the cilia circadian transcripts deviated from the phase of the majority of the background circadian transcripts, and transcripts coding for cilia basal body components accounted for the majority of cilia circadian transcripts. In addition, adjacent or functionally connected brain nuclei had large overlapping complements of circadian cilia genes. Most remarkably, cilia circadian transcripts shared across the basal ganglia nuclei and the prefrontal cortex peaked in these structures in sequential fashion that is similar to the sequential order of activation of the basal ganglia-cortical circuitry in connection with movement coordination, albeit on completely different timescales. These findings support a role for the circadian spatiotemporal orchestration of cilia gene expression in the normal physiology of the basal ganglia-cortical circuit and motor control. Studying orchestrated cilia rhythmicity in the basal ganglia-cortical circuits and other brain circuits may help develop better functional models, and shed light on the causal effects cilia functions have on these circuits and on the regulation of movement and other behaviors.