Spatiotemporal transcriptomic divergence across human and macaque brain development

• Published in: Science (American Association for the Advancement of Science) Vol. 362; no. 6420
• Main Authors: Zhu, Ying, Sousa, André M M, Gao, Tianliuyun, Skarica, Mario, Li, Mingfeng, Santpere, Gabriel, Esteller-Cucala, Paula, Juan, David, Ferrández-Peral, Luis, Gulden, Forrest O, Yang, Mo, Miller, Daniel J, Marques-Bonet, Tomas, Imamura Kawasawa, Yuka, Zhao, Hongyu, Sestan, Nenad
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 14.12.2018; American Association for the Advancement of Science (AAAS)
• Subjects: Adolescents; Adults; Age; Animals; Autism; Autism Spectrum Disorder - genetics; Biological evolution; Brain; Brain - embryology; Brain - growth & development; Child development; Cognition; Disorders; Divergence; Embryogenesis; Evolution; Fetuses; Gene expression; Gene Expression Regulation, Developmental; Gene regulation; Genes; Human behavior; Humans; Macaca mulatta; Mental disorders; Meta Analysis; Molecular modelling; Nervous system; Neural networks; Neurogenesis - genetics; Nuclei (cytology); Ontogeny; Pathogenesis; Phylogenetics; Phylogeny; Prefrontal cortex; Prefrontal Cortex - enzymology; Prefrontal Cortex - growth & development; Primates; Regional analysis; Regional development; Schizophrenia; Schizophrenia - genetics; Species; Temporal cortex; Tissues; Transcription; Transcriptome; Uniqueness
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aat8077

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.