Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Science. 2018 Dec 14;362(6420). doi: 10.1126/science.aat8077. Epub 2018 Dec 13.
Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.
人类神经系统的发育是一个复杂而漫长的过程，需要精确的时空转录调控。我们从多达 16 个大脑区域生成了组织水平和单细胞转录组数据，这些区域涵盖了恒河猴从产前到产后的发育过程。与人类互补数据的综合分析表明，全球种内（个体发生）和种间（系统发生）的区域转录组差异表现出协同的杯状模式，具有晚胎儿到婴儿期（围产期）的收敛。产前皮质的转录组模式显示出短暂的地形梯度，而产后模式则主要反映了功能层次。表现出异位和异时性差异的基因包括那些在产前前额叶皮质短暂富集的基因，或与自闭症谱系障碍和精神分裂症有关的基因。我们的研究结果为人类大脑发育进化和神经精神疾病发病机制的转录组程序提供了线索。
