Quantitative expression profile of distinct functional regions in the adult mouse brain.

Quantitative expression profile of distinct functional regions in the adult mouse brain.
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DOI:
10.1371/journal.pone.0023228
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Ueda HR
Ueda HR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kasukawa T;Masumoto KH;Nikaido I;Nagano M;Uno KD;Tsujino K;Hanashima C;Shigeyoshi Y;Ueda HR

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成年哺乳动物的大脑由不同的区域组成,这些区域具有特殊的作用,包括调节生物钟、摄食、睡眠/清醒和季节节律。为了找出不同大脑区域之间表达的定量差异,我们进行了BrainStars(B*)项目,在该项目中,我们描绘了∼50个小脑区的基因组范围的表达,包括感觉中心,以及运动、时间、记忆、恐惧和进食中心。为了避免基因表达的时间差异造成的混乱,我们每隔4小时对每个区域进行24小时的采样,并将样本汇集在一起进行DNA微阵列分析。因此,我们重点研究了基因表达的空间差异。我们使用信息学来识别在特定区域具有高或低表达的表达变化的候选基因。我们还发现了跨大脑区域稳定表达的候选基因,这些基因可以作为新的内部控制基因,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个区域标记基因候选的44个小脑区,915个内部对照基因候选,以及23864个推测的配体-受体相互作用。我们还发现,这些集合包括众所周知的基因以及可能与大脑区域特定功能相关的新候选基因。我们利用我们的发现开发了一个集成数据库(http://brainstars.org/)),用于探索成年小鼠大脑中全基因组的表达,并已使该数据库公开可用。这些新的资源将有助于加快哺乳动物大脑的功能分析和阐明其调控网络系统。
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.
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