Brown Laurence A, Williams John, Taylor Lewis, Thomson Ross J, Nolan Patrick M, Foster Russell G, Peirson Stuart N
Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 3RE, UK.
MRC Harwell Institute, Harwell Campus, Oxfordshire OX11 0RD, UK.
Nucleic Acids Res. 2017 Sep 29;45(17):9860-9873. doi: 10.1093/nar/gkx714.
The master circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) which regulate physiology and behaviour, as well as coordinating peripheral clocks throughout the body. Investigating the function of the SCN has often focused on the identification of rhythmically expressed genes. However, not all genes critical for SCN function are rhythmically expressed. An alternative strategy is to characterize those genes that are selectively enriched in the SCN. Here, we examined the transcriptome of the SCN and whole brain (WB) of mice using meta-analysis of publicly deposited data across a range of microarray platforms and RNA-Seq data. A total of 79 microarrays were used (24 SCN and 55 WB samples, 4 different microarray platforms), alongside 17 RNA-Seq data files (7 SCN and 10 WB). 31 684 MGI gene symbols had data for at least one platform. Meta-analysis using a random effects model for weighting individual effect sizes (derived from differential expression between relevant SCN and WB samples) reliably detected known SCN markers. SCN-enriched transcripts identified in this study provide novel insights into SCN function, including identifying genes which may play key roles in SCN physiology or provide SCN-specific drivers.
哺乳动物的主昼夜节律起搏器位于视交叉上核(SCN),它调节生理和行为,并协调全身的外周生物钟。对视交叉上核功能的研究通常集中在对节律性表达基因的鉴定上。然而,并非所有对视交叉上核功能至关重要的基因都是节律性表达的。另一种策略是对那些在视交叉上核中选择性富集的基因进行表征。在这里,我们通过对一系列微阵列平台和RNA测序数据的公开数据进行荟萃分析,研究了小鼠视交叉上核和全脑(WB)的转录组。总共使用了79个微阵列(24个视交叉上核和55个全脑样本,4种不同的微阵列平台),以及17个RNA测序数据文件(7个视交叉上核和10个全脑)。31684个MGI基因符号在至少一个平台上有数据。使用随机效应模型对个体效应大小(源自相关视交叉上核和全脑样本之间的差异表达)进行加权的荟萃分析可靠地检测到了已知的视交叉上核标记。本研究中鉴定出的视交叉上核富集转录本对视交叉上核功能提供了新的见解,包括鉴定可能在视交叉上核生理学中起关键作用或提供视交叉上核特异性驱动因素的基因。