Diurnal transcriptome atlas of a primate across major neural and peripheral tissues.
Diurnal transcriptome atlas of a primate across major neural and peripheral tissues.
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DOI：
10.1126/science.aao0318
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发表时间：
2018-03-16
期刊：
影响因子：
--
通讯作者：
Panda S
中科院分区：
文献类型：
--
作者：
Mure LS;Le HD;Benegiamo G;Chang MW;Rios L;Jillani N;Ngotho M;Kariuki T;Dkhissi-Benyahya O;Cooper HM;Panda S
细胞自主昼夜节律振荡器之间的相互作用——活动-休息和进食-禁食的每日循环——在几乎所有动物组织中产生基因表达的昼夜节律。这些节律控制着不同器官和大脑区域的各种功能的时间，提供最佳的健康。这些节律的慢性破坏是许多疾病和情感障碍的标志。在有限数量的啮齿动物组织中进行的时间序列基因表达研究表明，10%至40%的基因组以组织特异性的方式表现出约24小时的表达节奏。然而，来自人类或我们最近的灵长类亲戚的不同组织和大脑区域的节律表达数据是罕见的。这种多组织的昼夜基因表达数据对于了解基因表达的时空协调如何维持正常生理和行为的机制是必要的。我们使用RNA测序技术来评估狒狒（一种与人类密切相关的灵长类动物）在24小时光照-黑暗和喂食-禁食计划下的主要组织和大脑区域的基因表达。我们评估了雄性狒狒64个不同组织和大脑区域的基因表达，这些数据在24小时内每2小时收集一次。狒狒的组织特异性转录组与人类的可比较（Human GTEx数据集）。我们检测到bb0 25,000个表达转录物，包括蛋白质编码rna和非编码rna。近11000个基因在所有组织中普遍表达。这些普遍表达基因（UEGs）编码基本的细胞功能，如转录、RNA加工、DNA修复、蛋白质稳态和细胞代谢。其余基因在不同的组织中表达，约有1500个基因在单个组织中完全表达。在所有组织中都发现了节律转录本，但在一个组织中循环转录本的数量从200个到3000个不等，组织间节律转录本的曲目只有有限的重叠。在11000例ueg中，绝大多数（96.6%）至少在一个组织中表现出24小时节律性。在检测到的18,000个蛋白质编码基因中，大多数（bbb80 %）也表现出24小时的表达节律。组织中最丰富的节律转录本是核心时钟成分及其直接输出目标。然而，它们的日常节律的相对丰度和稳健性在不同组织中有所不同。考虑到有机体水平，64个组织的全球节律转录在清晨和下午晚些时候组织成峰值转录爆发（此时11,000个转录物达到峰值水平）。相比之下，在傍晚的相对“静止阶段”，也就是睡眠开始和不进食的时候，只有700个节律转录本达到了它们的峰值表达水平。80%的蛋白质编码基因的日常表达节律，编码多种生化和细胞功能，构成了迄今为止最大的整合细胞内和细胞间多种生化功能的调控机制。从翻译的角度来看，节律性可能对健康有重大影响，因为82.2%的编码蛋白质的基因被美国食品和药物管理局鉴定为可药物靶标，在转录中表现出周期性变化。灵长类动物的时空基因表达图谱。（左）对24小时内64个昼夜活动的灵长类动物组织的基因表达分析表明，82%的蛋白质编码基因在至少一个组织中是有节律的。（右）节律性表达是组织特异性的，并赋予给定组织的转录组一个额外的调节和身份层。
The interaction among cell-autonomous circadian oscillators—daily cycles of activity–rest and feeding–fasting—produces diurnal rhythms in gene expression in almost all animal tissues. These rhythms control the timing of a wide range of functions across different organs and brain regions, affording optimal fitness. Chronic disruption of these rhythms predisposes to and are hallmarks of numerous diseases and affective disorders. Time-series gene expression studies in a limited number of tissues from rodents have shown that 10 to 40% of the genome exhibits a ~24-hour rhythm in expression in a tissue-specific manner. However, rhythmic expression data from diverse tissues and brain regions from humans or our closest primate relatives is rare. Such multitissue diurnal gene expression data are necessary for gaining mechanistic understanding of how spatiotemporal orchestration of gene expression maintains normal physiology and behavior. We used a RNA sequencing technique to assess gene expression in major tissues and brain regions from baboons (a primate closely related to humans) housed under a defined 24-hour light– dark and feeding–fasting schedule. We assessed gene expression in 64 different tissues and brain regions of male baboons, collected every 2 hours over the 24-hour day. Tissue-specific transcriptomes in baboon were comparable with that from humans (Human GTEx data set). We detected >25,000 expressed transcripts, including protein-coding and -noncoding RNAs. Nearly 11,000 genes were commonly expressed in all tissues. These universally expressed genes (UEGs) encoded for basic cellular functions such as transcription, RNA processing, DNA repair, protein homeostasis, and cellular metabolism. The remainders were expressed in distinct sets of tissues, with ~1500 genes expressed exclusively in a single tissue. Rhythmic transcripts were found in all tissues, but the number of cycling transcripts varied from ~200 to >3000 in a given tissue, with only limited overlap in the repertoire of rhythmic transcripts between tissues. Of the 11,000 UEGs, the vast majority (96.6%) showed 24-hour rhythmicity in at least one tissue. A majority (>80%) of the 18,000 protein-coding genes detected also exhibited 24-hour rhythms in expression. The most enriched rhythmic transcripts across tissues were core clock components and their immediate output targets. However, their relative abundance and robustness of daily rhythms varied across tissues. Considered at the organismal level, global rhythmic transcription in 64 tissues organized into bursts of peak transcription, during early morning and late afternoon (when 11,000 transcripts reach their peak level). By contrast, during a relative “quiescent phase” in early evening that coincides with the onset of sleep and no food intake, only 700 rhythmic transcripts reach their peak expression level. The daily expression rhythms in >80% of protein-coding genes, encoding diverse biochemical and cellular functions, constitutes by far the largest regulatory mechanism that integrates diverse biochemical functions within and across cell types. From a translational point of view, rhythmicity may have a major impact in health because 82.2% of genes coding for proteins that are identified as druggable targets by the U.S. Food and Drug Administration show cyclic changes in transcription. Spatiotemporal gene expression atlas of a primate. (Left) Gene expression analysis across 64 tissues of a diurnal primate sampled over the 24-hour day shows that 82% of protein-coding genes are rhythmic in at least one tissue. (Right) Rhythmic expression is tissue-specific and confers an additional layer of regulation and identity to the transcriptome of a given tissue.
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影响因子：
29
作者：
Vollmers C;Schmitz RJ;Nathanson J;Yeo G;Ecker JR;Panda S
通讯作者：
Panda S
影响因子：
56.9
作者：
Harmer, SL;Hogenesch, LB;Kay, SA
通讯作者：
Kay, SA
影响因子：
64.8
作者：
Ueda, HR;Chen, WB;Hashimoto, S
通讯作者：
Hashimoto, S
影响因子：
5.8
作者：
Wu, Gang;Anafi, Ron C.;Hogenesch, John B.
通讯作者：
Hogenesch, John B.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium