Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

与认知能力和 HAR 相关的基因在人类皮质神经元类型中表现出重叠的表达模式

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作者:Stan L W Driessens #, Anna A Galakhova #, Djai B Heyer #, Isabel J Pieterse, René Wilbers, Eline J Mertens, Femke Waleboer, Tim S Heistek, Loet Coenen, Julia R Meijer, Sander Idema, Philip C de Witt Hamer, David P Noske, Christiaan P J de Kock, Brian R Lee, Kimberly Smith, Jonathan T Ting, Ed S Lein

Abstract

GWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 pyramidal neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger total dendritic length (TDL) and faster action potential (AP) kinetics, properties previously linked to intelligence. We identify a subset of genes associated with TDL or AP kinetics with predominantly synaptic functions and high abundance of HARs.

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