Integrative functional genomic analysis of human brain development and neuropsychiatric risks
Integrative functional genomic analysis of human brain development and neuropsychiatric risks
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DOI：
10.1126/science.aat7615
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发表时间：
2018-12-14
期刊：
影响因子：
56.9
通讯作者：
Sanders, Stephan
中科院分区：
文献类型：
--
作者：
Li, Mingfeng;Santpere, Gabriel;Sanders, Stephan
为了扩大我们对人类神经发育的理解，我们分析了整个产前和产后发育过程中大脑区域和/或细胞类型的转录组和表观基因组景观。综合分析揭示了时间，区域，性别和细胞类型的特定动态。我们观察到一个全球的转录杯形模式，其特征是一个晚期胎儿过渡与急剧减少的区域差异和细胞组成和成熟的变化，随后在儿童期-青春期逆转，并伴随着表观基因组重组。基因共表达模块的分析揭示了与表观基因组调控和神经发育过程的关系。与基于大脑的特征和神经精神疾病（包括MEF 2C，SATB 2，SOX 5，TCF 4和TSHZ 3）遗传相关的基因在少数模块和不同的细胞类型中聚集，揭示了对神经发育和神经精神风险的基因组基础的见解。
To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.