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RNA 测序显示,在心脏起搏器的转录组中存在一种普遍的昼夜节律。

RNAseq shows an all-pervasive day-night rhythm in the transcriptome of the pacemaker of the heart.

机构信息

Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.

Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.

出版信息

Sci Rep. 2021 Feb 11;11(1):3565. doi: 10.1038/s41598-021-82202-7.

Abstract

Physiological systems vary in a day-night manner anticipating increased demand at a particular time. Heart is no exception. Cardiac output is primarily determined by heart rate and unsurprisingly this varies in a day-night manner and is higher during the day in the human (anticipating increased day-time demand). Although this is attributed to a day-night rhythm in post-translational ion channel regulation in the heart's pacemaker, the sinus node, by the autonomic nervous system, we investigated whether there is a day-night rhythm in transcription. RNAseq revealed that ~ 44% of the sinus node transcriptome (7134 of 16,387 transcripts) has a significant day-night rhythm. The data revealed the oscillating components of an intrinsic circadian clock. Presumably this clock (or perhaps the master circadian clock in the suprachiasmatic nucleus) is responsible for the rhythm observed in the transcriptional machinery, which in turn is responsible for the rhythm observed in the transcriptome. For example, there is a rhythm in transcripts responsible for the two principal pacemaker mechanisms (membrane and Ca clocks), transcripts responsible for receptors and signalling pathways known to control pacemaking, transcripts from genes identified by GWAS as determinants of resting heart rate, and transcripts from genes responsible for familial and acquired sick sinus syndrome.

摘要

生理系统会按照日夜模式变化,以预测特定时间的需求增加。心脏也不例外。心输出量主要由心率决定,而心率在日夜模式中变化,在人类中白天更高(预计白天需求增加)。尽管这归因于自主神经系统对心脏起搏器窦房结的翻译后离子通道调节的日夜节律,但我们研究了转录是否存在日夜节律。RNAseq 显示,窦房结转录组的~44%(16387 个转录本中的 7134 个)具有明显的日夜节律。这些数据揭示了内在生物钟的振荡成分。大概这个时钟(或者可能是视交叉上核中的主生物钟)负责观察到的转录机制中的节律,而转录机制又负责观察到的转录组中的节律。例如,有节奏的转录本负责两个主要的起搏机制(膜和 Ca 时钟),负责控制起搏的受体和信号通路的转录本,从 GWAS 确定为静息心率决定因素的基因的转录本,以及负责家族性和获得性窦房结疾病的基因的转录本。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93e2/7878777/065d63534029/41598_2021_82202_Fig1_HTML.jpg

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