Genes to Cognition Programme, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Elife. 2017 Sep 12;6:e17915. doi: 10.7554/eLife.17915.
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.
调控大脑和行为的遗传机制在整个生命周期中都知之甚少。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时间表。转录组轨迹定义了神经元、神经胶质细胞和内皮细胞类型中基因表达变化的顺序，这使得能够根据组织样本预测年龄。寿命的一个主要里程碑是人类在 26 岁和小鼠在 5 个月大时轨迹变化的峰值。这个在物种间保守的峰值在女性中延迟，并标志着突触和精神分裂症易感性基因表达的重新组织。寿命日历预测了年轻人中精神分裂症的发病特征年龄和性别差异。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，该日历定时大脑依赖年龄的分子组织，以及在年轻人中中断该程序的突变导致精神分裂症。
