A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia
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DOI：
10.7554/elife.17915
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发表时间：
2017-09-12
期刊：
影响因子：
7.7
通讯作者：
Grant, Seth G. N.
中科院分区：
文献类型：
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作者：
Skene, Nathan G.;Roy, Marcia;Grant, Seth G. N.
在整个生命周期中调节大脑和行为的遗传机制尚不清楚。我们发现寿命转录组轨迹描述了人类和小鼠大脑中基因调控事件的日历。转录组轨迹定义了神经元、神经胶质和内皮细胞类型中基因表达变化的序列，从而能够从组织样本中预测年龄。一个重要的生命里程碑是人类在26岁和小鼠在5个月大时轨迹变化的峰值。这个物种保守的峰值在雌性中延迟，标志着突触和精神分裂症易感基因的表达重组。寿命日历预测了年轻人发病的典型年龄和精神分裂症的性别差异。我们提出了一个基因组程序，生成一个基因调控的寿命日历，该日历将与年龄相关的大脑分子组织和中断该程序的突变在年轻人中导致精神分裂症。
The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.