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Science. 2017 Nov 24;358(6366):1027-1032. doi: 10.1126/science.aan3456.

Molecular and cellular reorganization of neural circuits in the human lineage.

Author information

1
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
2
Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, OH, USA.
3
Program in Computational Biology and Bioinformatics, Departments of Molecular Biophysics and Biochemistry and Computer Science, Yale University, New Haven, CT, USA.
4
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
5
Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
6
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, New Haven, CT, USA.
7
Departments of Pharmacology and Biochemistry and Molecular Biology, Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA.
8
Institut de Biologia Evolutiva, Consejo Superior de Investigaciones Científicas, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona, Catalonia, Spain.
9
Alamogordo Primate Facility, Holloman Air Force Base, NM, USA.
10
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
11
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
12
Neuroscience Program, Michigan State University, East Lansing, MI, USA.
13
Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
14
Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
15
Laboratory of Human Genetics and Genomics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
16
Yale Center for Genomic Analysis, Yale School of Medicine, New Haven, CT, USA.
17
Department of Psychiatry and Langley Porter Psychiatric Institute, University of California, San Francisco, San Francisco, CA, USA.
18
Allen Institute for Brain Science, Seattle, WA, USA.
19
Department of Psychiatry and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
20
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
21
Centro Nacional de Analisis Genomico, Barcelona, Catalonia, Spain.
22
Department of Anthropology, The George Washington University, Washington, DC, USA.
23
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA. nenad.sestan@yale.edu.
24
Program in Cellular Neuroscience, Neurodegeneration, and Repair and Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA.

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.

PMID:
29170230
PMCID:
PMC5776074
DOI:
10.1126/science.aan3456
[Indexed for MEDLINE]
Free PMC Article

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