Association of gene expression and brain connectivity in human cerebral cortex development and adulthood

摘要 构成人类功能电路和全球网络组织的细胞到细胞的连接 大脑在根本上具有精确的基因表达时空模式，这些模式区分大脑区域、细胞 类型和发育时期。最近的发现揭示了高度动态的时空模式 基因在整个发育过程和大脑的几个区域中的表达，但阐明了神经 连接体--所有神经连接的综合图谱--在人类发育的多个年龄段， 直到最近，这还不是很实际。因此，尽管我们现在对转录的理解很深 在发育中的和成年的人脑中的重组，这些动力学如何调节其他关键现象 对大脑功能至关重要的，如神经连接，还没有被很好地理解。作为特定地区的中断， 神经连接可能是包括精神分裂症和自闭症在内的神经精神障碍的基础 无序，转录组信息与连接性的关联是分析的关键下一个前沿。我们 因此，建议基于神经MRI和收集的转录组数据来整合人脑连接组 以前所未有的空间分辨率跨越人类出生后发育的多个时间点 候选基因、基因表达模块、大脑区域、发育周期和连接模式 与人类大脑的发育有关。为了实现这一点，我们将开发一种高分辨率的连通图集 利用独特的现有发育和成人数据以及来自 儿童早期和晚期是通过其他来源获得的。本地图集将与转录地图集配对 来自出生后的人类新皮质，由25个新皮质区域组成，并将与公共 在单细胞水平上产生的现有的、不太全面的转录数据。最后，我们将验证 我们揭示的基因表达模式和关联，并通过免费传播图谱和数据集 一个集成的门户网站。

ABSTRACT The cell-to-cell connections that comprise the functional circuitry and global network organization of the human brain have at their root precise spatiotemporal patterns of gene expression that differentiate brain regions, cell types, and developmental periods. Recent discoveries have revealed highly dynamic spatiotemporal patterns of gene expression throughout development and in several regions of the brain, but elucidating the neural connectome – the comprehensive map of all neural connections – at multiple ages of human development has, until recently, not been practical. Consequently, although we now have a strong understanding of transcriptional reorganizations in the developing and adult human brain, how these dynamics mediate other key phenomena essential for brain function, such as neural connectivity, is not well understood. As region-specific disruptions to neural connectivity may underlie neuropsychiatric disorders including schizophrenia and autism spectrum disorder, the association of transcriptome information with connectivity is a critical next frontier for analysis. We therefore propose to integrate human brain connectome based on neural MRI and transcriptome data collected across multiple timepoints in human postnatal development with unprecedented spatial resolution to implicate candidate genes, gene expression modules, brain regions, developmental periods, and connectivity patterns with human brain development. To accomplish this, we will develop a high-resolution connectome atlas established with unique existing developmental and adult data as well as next-generation connectome data from early and late childhood being acquired with other sources. This atlas will be paired with transcriptomic atlas from the postnatal human neocortex consisting of 25 neocortical areas and will be integrated with publicly available, less comprehensive transcriptomic data generated at the level of the single cell. Finally, we will validate gene expression patterns and the associations we reveal, and freely disseminate atlases and datasets through an integrated web portal.