Spatio-temporal transcriptome of the human brain

Hyo Jung Kang, Yuka Imamura Kawasawa, Feng Cheng, Ying Zhu, Xuming Xu, Mingfeng Li, André M. M. Sousa, Mihovil Pletikos, Kyle A. Meyer, Goran Sedmak, Tobias Guennel, Yurae Shin, Matthew B. Johnson, Željka Krsnik, Simone Mayer, Sofia Fertuzinhos, Sheila Umlauf, Steven N. Lisgo, Alexander Vortmeyer, Daniel R. Weinberger, Shrikant Mane, Thomas M. Hyde, Anita Huttner, Mark Reimers, Joel E. Kleinman and Nenad Šestan ()
Additional contact information
Hyo Jung Kang: Yale University School of Medicine
Yuka Imamura Kawasawa: Yale University School of Medicine
Feng Cheng: Yale University School of Medicine
Ying Zhu: Yale University School of Medicine
Xuming Xu: Yale University School of Medicine
Mingfeng Li: Yale University School of Medicine
André M. M. Sousa: Yale University School of Medicine
Mihovil Pletikos: Yale University School of Medicine
Kyle A. Meyer: Yale University School of Medicine
Goran Sedmak: Yale University School of Medicine
Tobias Guennel: Virginia Commonwealth University
Yurae Shin: Yale University School of Medicine
Matthew B. Johnson: Yale University School of Medicine
Željka Krsnik: Yale University School of Medicine
Simone Mayer: Yale University School of Medicine
Sofia Fertuzinhos: Yale University School of Medicine
Sheila Umlauf: Yale Center for Genome Analysis, Yale University School of Medicine
Steven N. Lisgo: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK
Alexander Vortmeyer: Yale University School of Medicine
Daniel R. Weinberger: Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health
Shrikant Mane: Yale Center for Genome Analysis, Yale University School of Medicine
Thomas M. Hyde: Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health
Anita Huttner: Yale University School of Medicine
Mark Reimers: Virginia Commonwealth University
Joel E. Kleinman: Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health
Nenad Šestan: Yale University School of Medicine

Nature, 2011, vol. 478, issue 7370, 483-489

Abstract: Abstract Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.

Date: 2011
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DOI: 10.1038/nature10523

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