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Spatio-temporal transcriptome of the human brain

Lookup NU author(s): Dr Steven LisgoORCiD

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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.


Publication metadata

Author(s): Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu XM, Li MF, Sousa AMM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N

Publication type: Article

Publication status: Published

Journal: Nature

Year: 2011

Volume: 478

Issue: 7370

Pages: 483-489

Print publication date: 26/10/2011

ISSN (print): 0028-0836

ISSN (electronic): 1476-4687

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/nature10523

DOI: 10.1038/nature10523


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Funding

Funder referenceFunder name
China Scholarship Council
James S. McDonnell Foundation
NARSAD
German Academic Exchange Service - DAAD
Kavli Foundation
Portuguese Foundation for Science and Technology
Samsung Scholarship Foundation
DA026119NIDA
HD000836Eunice Kennedy Shriver National Institute of Child Health and Human Development
G0700089
GR082557
MH081896US National Institutes of Health
MH089929US National Institutes of Health
NS054273US National Institutes of Health

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