大脑高级功能相关基因的系统生物学分析

The identification of brain advanced function associated genes is a cutting edge research area in neuroscience, bringing the connections with brain functional signal and its underling molecular activities. In previous research, we have identified genes which expression levels are correlated with brain resting-state functional activities independently with another research group. The results of the two groups are significantly overlapped, implicating the robustness of the analysis. Subsequently, by exploring a similar approach, we revealed a group of genes the expression of which are correlated with memory effects in large-scale memory encoding experiments of patients. Those prior studies outlined some essential properties of brain advanced function associated genes, that is, they prefer to be expressed in neurons, especially in interneurons. Meanwhile they are highly enriched in Autism genes or modules, suggesting their potential role in brain development. In this study we propose to perform systems analysis on the expression of those genes spatially and temporally in both human and non-human primates. We sought to identify their potential regulatory modules by using network approach. This research will provide molecular basis for understanding human brain advanced function, and find new clues for the treatment of neurodevelopmental diseases such as Autism.

大脑高级功能相关基因的鉴定与分析是神经科学的一个前沿领域。通过把脑活动信号和分子水平上的活动信号联系起来，我们与其他研究组独立鉴定了与大脑静息态相关的的基因，两者的结果有很好的重复性。应用类似的办法，我们又进一步鉴定了与学习记忆编码过程相关的基因，并发现这些基因倾向于在中间神经元中高表达，而且和自闭症等疾病有很多联系。本课题中，我们将系统的分析这些脑高级功能相关基因在人脑以及灵长类大脑各个脑区和各个发育过程中，以及网络水平上的调控模式等。本项目的成功实施将会为理解大脑高级功能的遗传学基础提供新的证据，并且为神经发育性疾病的治疗提供新的思路。

全面刻画大脑高级功能有关的基因特征对于理解大脑高级功能的遗传基础有着重要的意义。我们通过系统生物学全面的分析，发现大脑发育过程中存在着双峰发育模式，并且大脑高级功能有关的基因广泛参与其中，这些过程与认知以及脑疾病有关基因深度关联。通过对单细胞层面的分析，我们发现神经元细胞，尤其是兴奋性神经元细胞的进化约束大于其他神经细胞类型的，并且不同的细胞类型富集到不同的发育阶段。这些为脑发育早期的进一步建模打下了基础。