Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development.

与其他灵长类动物相比，人类拥有更长的幼年期，该阶段大脑具有更强的可塑性。本研究旨在围绕这一适应性可塑性，探究发育过程中大脑皮层的基因表达情况。我们开发了一种能够区分基因表达模式呈变异型与恒定型的分析方法，并发现儿童群体的基因表达个体间差异显著高于成人群体。针对呈现该表达模式的337个转录本（transcripts），我们发现被注释为参与免疫系统过程的基因出现了显著富集现象（假发现率pFDR≅0）。此外，在儿童期表达变异程度更高的基因中，还包含了已知对神经元功能至关重要的基因，例如脑源性神经营养因子（BDNF）。我们提出，与大脑可塑性降低的成年期相比，儿童期神经元可塑性增强的发育阶段，其大脑皮层的基因表达模式更为动态。此类基因中大量被注释为参与免疫系统过程，这表明这些基因的功能不仅可从抗原加工与呈递的角度解读，还可关联至神经系统发育的语境中。