Functional Genomics Unit, RIKEN Center for Developmental Biology, Kobe, Hyogo, Japan.
PLoS One. 2011;6(8):e23228. doi: 10.1371/journal.pone.0023228. Epub 2011 Aug 12.
The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.
成年哺乳动物大脑由具有特定功能的不同区域组成,包括调节生物钟、进食、睡眠/觉醒和季节性节律。为了发现这些不同脑区之间表达的定量差异,我们进行了 BrainStars(B*)项目,在该项目中,我们对约 50 个小脑区的全基因组表达进行了分析,包括感觉中心、运动中心、时间中心、记忆中心、恐惧中心和进食中心。为了避免基因表达时间差异带来的干扰,我们每 4 小时从每个区域采样一次,持续 24 小时,并将样本混合进行 DNA 微阵列分析。因此,我们专注于基因表达的空间差异。我们使用信息学方法来识别具有特定区域高表达或低表达的候选基因。我们还鉴定了在大脑区域中稳定表达的候选基因,可以用作新的内参基因,以及神经激素和神经递质的配体-受体相互作用。通过这些分析,我们发现了 8159 个多态基因、2212 个用于 44 个小脑区的区域标记基因候选物、915 个内参基因候选物和 23864 个推断的配体-受体相互作用。我们还发现,这些基因集包括已知基因和新的候选基因,它们可能与特定脑区的特定功能有关。我们利用这些发现开发了一个整合数据库(http://brainstars.org/),用于探索成年小鼠大脑的全基因组表达,并公开提供了这个数据库。这些新资源将有助于加速哺乳动物大脑的功能分析和其调控网络系统的阐明。