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. WeinbergerShrikant Mane, Thomas M. Hyde, Anita Huttner, Mark Reimers, Joel E. Kleinman, Nenad Šestan

Research output: Contribution to journalArticle

936 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalNature
Volume478
Issue number7370
DOIs
StatePublished - Oct 27 2011
Externally publishedYes

ASJC Scopus subject areas

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    Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., Guennel, T., Shin, Y., Johnson, M. B., Krsnik, Ž., Mayer, S., Fertuzinhos, S., Umlauf, S., Lisgo, S. N., Vortmeyer, A., ... Šestan, N. (2011). Spatio-temporal transcriptome of the human brain. Nature, 478(7370), 483-489. https://doi.org/10.1038/nature10523