Accelerated evolution of oligodendrocytes in the human brain

• Type of Material: Article
• Authors: Stefano Berto, University of Texas Southwestern Medical Center; Isabel Mendizabal, Georgia Institute of Technology; Noriyoshi Usui, University of Texas Southwestern Medical Center; Kazuya Toriumi, University of Texas Southwestern Medical Center; Paramita Chatterjee, Georgia Institute of Technology; Connor Douglas, University of Texas Southwestern Medical Center; Carol A. Tamminga, University of Texas Southwestern Medical Center; Todd Preuss, Emory University; Soojin V. Yi, Georgia Institute of Technology; Genevieve Konopka, University of Texas Southwestern Medical Center
• Language: English
• Date: 2019-11-26
• Publisher: United States National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2019 National Academy of Sciences.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1907982116
• Title of Journal or Parent Work: PNAS
• Volume: 116
• Issue: 48
• Start Page: 24334
• End Page: 24342
• Grant/Funding Information: Human tissue samples were obtained from the NIH NeuroBioBank (The Harvard Brain Tissue Resource Center, funded through HHSN-271-2013-00030C, the Human Brain and Spinal Fluid Resource Center, VA West Los Angeles Healthcare Center; and the University of Miami Brain Endowment Bank) and the UT Neuropsychiatry Research Program (Dallas Brain Collection).; Nonhuman primate tissue samples were obtained from Yerkes National Primate Research Center (P51OD11132).; This work was supported by the Uehara Memorial Foundation to N.U.; the Japan Society for the Promotion of Science (JSPS) Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (S2603) to N.U., K.T., S.B. and G.K.; the National Chimpanzee Brain Resource, NIH R24NS092988, the NIH National Center for Research Resources P51RR165 (superceded by the Office of Research Infrastructure Programs/OD P51OD11132) to T.M.P.; the National Science Foundation (SBE-131719) to S.V.Y.; the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition – Scholar Award to G.K.; and the National Institute of Mental Health (MH103517), to T.M.P., G.K., and S.V.Y.
• Keywords: RNA; Loci; Architecture; Primate; Science & Technology - Other Topics; Association; cell-type expression; Myelination; Old-world monkeys; Multidisciplinary Sciences; brain evolution; Science & Technology; neurogenomics; comparative primate genomics; Transcription; Expression analysis; Phylogeny
• Research Categories: Biology, Cell; Health Sciences, Pathology; Biology, Neuroscience; Psychology, Behavioral

Abstract

Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow similar or distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in neurons and oligodendrocytes and show that both cell types exhibit human-specific up-regulation. Moreover, oligodendrocytes have undergone more pronounced accelerated gene expression evolution in the human lineage compared to neurons. We highlighted human-specific coexpression networks with specific functions. Our data suggest that oligodendrocyte human-specific networks are enriched for alternative splicing and transcriptional regulation. Oligodendrocyte networks are also enriched for variants associated with schizophrenia and other neuropsychiatric disorders. Such enrichments were not found in neuronal networks. These results offer a glimpse into the molecular mechanisms of oligodendrocytes during evolution and how such mechanisms are associated with neuropsychiatric disorders.