人类谱系中神经回路的分子与细胞重组。
Molecular and cellular reorganization of neural circuits in the human lineage.
作者信息
Sousa André M M, Zhu Ying, Raghanti Mary Ann, Kitchen Robert R, Onorati Marco, Tebbenkamp Andrew T N, Stutz Bernardo, Meyer Kyle A, Li Mingfeng, Kawasawa Yuka Imamura, Liu Fuchen, Perez Raquel Garcia, Mele Marta, Carvalho Tiago, Skarica Mario, Gulden Forrest O, Pletikos Mihovil, Shibata Akemi, Stephenson Alexa R, Edler Melissa K, Ely John J, Elsworth John D, Horvath Tamas L, Hof Patrick R, Hyde Thomas M, Kleinman Joel E, Weinberger Daniel R, Reimers Mark, Lifton Richard P, Mane Shrikant M, Noonan James P, State Matthew W, Lein Ed S, Knowles James A, Marques-Bonet Tomas, Sherwood Chet C, Gerstein Mark B, Sestan Nenad
机构信息
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, OH, USA.
出版信息
Science. 2017 Nov 24;358(6366):1027-1032. doi: 10.1126/science.aan3456.
To better understand the molecular and cellular differences in brain organization between human and nonhuman primates, we performed transcriptome sequencing of 16 regions of adult human, chimpanzee, and macaque brains. Integration with human single-cell transcriptomic data revealed global, regional, and cell-type-specific species expression differences in genes representing distinct functional categories. We validated and further characterized the human specificity of genes enriched in distinct cell types through histological and functional analyses, including rare subpallial-derived interneurons expressing dopamine biosynthesis genes enriched in the human striatum and absent in the nonhuman African ape neocortex. Our integrated analysis of the generated data revealed diverse molecular and cellular features of the phylogenetic reorganization of the human brain across multiple levels, with relevance for brain function and disease.
为了更好地理解人类与非人类灵长类动物大脑组织在分子和细胞层面的差异，我们对成年人类、黑猩猩和猕猴大脑的16个区域进行了转录组测序。将其与人类单细胞转录组数据整合后发现，在代表不同功能类别的基因中，存在全局、区域和细胞类型特异性的物种表达差异。我们通过组织学和功能分析，包括对表达多巴胺生物合成基因的罕见的源于皮质下的中间神经元进行分析，验证并进一步表征了不同细胞类型中富集基因的人类特异性，这些中间神经元在人类纹状体中富集，而在非洲猿类的新皮质中不存在。我们对所生成数据的综合分析揭示了人类大脑在多个层面上系统发育重组的多样分子和细胞特征，这与脑功能和疾病相关。
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