Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. Here, we assessed over 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. While most transcriptomically-defined cell subtypes are conserved, we detected several only in some species and substantial species-specific molecular differences across homologous neuronal, glial and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin (SST) and tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, in certain interneurons, and also by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer-4 granular neurons. We generated a comprehensive survey of dlPFC cellular repertoire and its shared and divergent features in anthropoid primates. Single-cell transcriptomics reveals prefrontal cell taxonomy and species differences in human, chimpanzee, macaque and marmoset.

颗粒状背外侧前额叶皮质（dlPFC）是灵长类动物的一种进化特化结构，在认知中起核心作用。在此，我们对来自成年人、黑猩猩、猕猴和狨猴的dlPFC的60多万个单核转录组进行了评估。虽然大多数由转录组定义的细胞亚型是保守的，但我们仅在某些物种中检测到几种细胞亚型，并且在同源的神经元、神经胶质和非神经亚型中发现了大量物种特异性的分子差异。后者的例子包括在某些中间神经元中，神经肽生长抑素（SST）和酪氨酸羟化酶（TH，多巴胺生成的限速酶）表达之间的人类特异性转换，以及神经精神疾病风险基因FOXP2的表达，它在小胶质细胞中是人类特异性的，在第4层颗粒神经元中是灵长类特异性的。我们对类人猿灵长类动物的dlPFC细胞组成及其共有和不同的特征进行了全面的调查。 单细胞转录组学揭示了人类、黑猩猩、猕猴和狨猴的前额叶细胞分类和物种差异。