Abstract:
The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain\'s language network.
摘要:
人类大脑的语言网络在额叶下皮层和上/中颞叶皮层具有核心组成部分,在大多数人的左半球占主导地位。这些新皮质区域的功能专业化和相互连通性可能反映在它们的分子和细胞谱中。皮层区域之间的兴奋连接根据层特定的模式出现并神经支配。这里,我们从核心语言网络区域的人类死后皮质组织样本中生成了一个基因表达数据集,使用空间转录组学区分皮质层的基因表达。将这些数据与现有的单细胞表达数据整合,确定了56个基因,这些基因显示了额叶和颞叶语言皮层之间的层状表达谱差异,以及II/III层和/或V/VI层兴奋性神经元的上调。根据大规模全基因组筛查的数据,这56个基因中的DNA变异显示了与左半球额叶和颞叶语言皮层之间结构连接的个体间变异的集合水平关联,以及与大脑相关的障碍阅读障碍和精神分裂症,这些障碍通常涉及受影响的语言。这些发现将层状基因表达的特定区域模式确定为大脑语言网络的特征。