Molecular and cellular reorganization of neural circuits in the human lineage

André M.M. Sousa, Ying Zhu, Mary Ann Raghanti, Robert R. Kitchen, Marco Onorati, Andrew T.N. Tebbenkamp, Bernardo Stutz, Kyle A. Meyer, Mingfeng Li, Yuka Imamura Kawasawa, Fuchen Liu, Raquel Garcia Perez, Marta Mele, Tiago Carvalho, Mario Skarica, Forrest O. Gulden, Mihovil Pletikos, Akemi Shibata, Alexa R. Stephenson, Melissa K. EdlerJohn J. Ely, John D. Elsworth, Tamas L. Horvath, Patrick R. Hof, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger, Mark Reimers, Richard P. Lifton, Shrikant M. Mane, James P. Noonan, Matthew W. State, Ed S. Lein, James A. Knowles, Tomas Marques-Bonet, Chet C. Sherwood, Mark B. Gerstein, Nenad Sestan

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1027-1032
Number of pages6
JournalScience
Volume358
Issue number6366
DOIs
StatePublished - Nov 24 2017

All Science Journal Classification (ASJC) codes

  • General

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    Sousa, A. M. M., Zhu, Y., Raghanti, M. A., Kitchen, R. R., Onorati, M., Tebbenkamp, A. T. N., Stutz, B., Meyer, K. A., Li, M., Kawasawa, Y. I., Liu, F., Perez, R. G., Mele, M., Carvalho, T., Skarica, M., Gulden, F. O., Pletikos, M., Shibata, A., Stephenson, A. R., ... Sestan, N. (2017). Molecular and cellular reorganization of neural circuits in the human lineage. Science, 358(6366), 1027-1032. https://doi.org/10.1126/science.aan3456