Kang, H. J. et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483-489

Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature (Impact Factor: 41.46). 10/2011; 478(7370):483-9. DOI: 10.1038/nature10523
Source: PubMed


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.

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Available from: Mark A Reimers, Dec 28, 2013
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    • "It plays a role in presynaptic plasticity (Kaeser et al., 2012), with mouse knockouts showing deficits in learning and memory (Powell et al., 2004) and increased seizure frequency following induced status epilepticus (Pitsch et al., 2012). RIMS1 is expressed throughout the human brain, with levels increasing throughout development and reaching a plateau in the third trimester that persists throughout adulthood (Kang et al., 2011). The gene is present in an ASD-associated postnatal coexpression network in the cerebellum and mediodorsal nucleus of the thalamus (8-10 MD- CBC) due to its coexpression with the ASD gene SCN2A (Willsey et al., 2013). "
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    Cell Reports 10/2014; 9(1). DOI:10.1016/j.celrep.2014.08.068 · 8.36 Impact Factor
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    • "Because FMRP is expressed in most neuronal subtypes from early fetal development to aging (Abitbol et al., 1993; Devys et al., 1993; Hinds et al., 1993; Kang et al., 2011), its spatiotemporal expression pattern does not implicate any particular neural structure or developmental stage to be especially important to the etiology of the disorder. Recent advances in the fields of ASD and SCZ genetics have, however, begun to reveal the neurobiology and neural substrates that underlie complex disorders of brain development. "
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    Frontiers in Genetics 07/2014; 5:239. DOI:10.3389/fgene.2014.00239
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    • "Transcriptomics studies have been instrumental for characterizing the development of model organisms, the human brain, or various stem cells (Kang et al. 2011; Mariani et al. 2012; Xie et al. 2013; Yang et al. 2013). Most available data refer to fixed time points, but some studies already showed the highly dynamic behavior of such systems (Theunissen et al. 2012; Zimmer et al. 2011). "
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