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Science. 2018 Dec 14;362(6420). pii: eaat8077. doi: 10.1126/science.aat8077. Epub 2018 Dec 13.

Spatiotemporal transcriptomic divergence across human and macaque brain development.

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Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Institute of Evolutionary Biology (UPF-CSIC), PRBB, Barcelona, Spain.
Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Barcelona, Spain.
Departments of Pharmacology and Biochemistry and Molecular Biology, Institute for Personalized Medicine, Penn State University College of Medicine, Hershey, PA, USA.
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Departments of Genetics, Psychiatry, and Comparative Medicine, Program in Cellular Neuroscience, Neurodegeneration and Repair, and Yale Child Study Center, Yale School of Medicine, New Haven, CT, USA.


Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.

[Indexed for MEDLINE]

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