Accelerated evolution of oligodendrocytes in the human brain
Accelerated evolution of oligodendrocytes in the human brain
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DOI：
10.1073/pnas.1907982116
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发表时间：
2019-11-26
影响因子：
11.1
通讯作者：
Konopka, Genevieve
中科院分区：
文献类型：
--
作者：
Berto, Stefano;Mendizabal, Isabel;Konopka, Genevieve
最近关于人类大脑进化的讨论主要集中在神经元数量的增加及其连接和表达的变化。然而，人们越来越认识到少突胶质细胞在认知功能和疾病中发挥着重要作用。这两种细胞类型是否遵循相似或独特的进化轨迹尚不清楚。我们检查了人类、黑猩猩和恒河猴额叶皮层神经元和少突胶质细胞的转录组。我们确定了神经元和少突胶质细胞中人类特异性的基因表达轨迹，并表明这两种细胞类型都表现出人类特异性的上调。此外，与神经元相比，少突胶质细胞在人类谱系中经历了更明显的加速基因表达进化。我们强调了具有特定功能的人类特异性共表达网络。我们的数据表明，少突胶质细胞人类特异性网络丰富了选择性剪接和转录调控。少突胶质细胞网络也富含与精神分裂症和其他神经精神疾病相关的变异。在神经元网络中没有发现这种富集。这些结果让我们了解少突胶质细胞在进化过程中的分子机制以及这些机制如何与神经精神疾病相关。
Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow similar or distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in neurons and oligodendrocytes and show that both cell types exhibit human-specific up-regulation. Moreover, oligodendrocytes have undergone more pronounced accelerated gene expression evolution in the human lineage compared to neurons. We highlighted human-specific coexpression networks with specific functions. Our data suggest that oligodendrocyte human-specific networks are enriched for alternative splicing and transcriptional regulation. Oligodendrocyte networks are also enriched for variants associated with schizophrenia and other neuropsychiatric disorders. Such enrichments were not found in neuronal networks. These results offer a glimpse into the molecular mechanisms of oligodendrocytes during evolution and how such mechanisms are associated with neuropsychiatric disorders.