1. Spatiotemporal transcriptome of the human brain
- Author
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Tobias Guennel, Kyle A. Meyer, Mark Reimers, Steven Lisgo, Yurae Shin, Matthew B. Johnson, Simone Mayer, Ying Zhu, André M. M. Sousa, Mihovil Pletikos, Daniel R. Weinberger, Sofia Fertuzinhos, Željka Krsnik, Thomas M. Hyde, Yuka Imamura Kawasawa, Mingfeng Li, Feng Cheng, Joel E. Kleinman, Alexander O. Vortmeyer, Goran Sedmak, Shrikant Mane, Xuming Xu, Hyo Jung Kang, Sheila Umlauf, Nenad Sestan, and Anita Huttner
- Subjects
Adult ,Quality Control ,Male ,Aging ,Time Factors ,Adolescent ,Quantitative Trait Loci ,Gene regulatory network ,Single-nucleotide polymorphism ,Computational biology ,Biology ,Article ,Transcriptome ,03 medical and health sciences ,Exon ,Young Adult ,0302 clinical medicine ,Fetus ,medicine ,Humans ,Gene Regulatory Networks ,gene expression ,brain development ,microarray ,human brain ,Child ,Gene ,030304 developmental biology ,Aged ,Genetics ,Regulation of gene expression ,Aged, 80 and over ,0303 health sciences ,Sex Characteristics ,Multidisciplinary ,Gene Expression Profiling ,human brain, transcriptome ,Infant ,Brain ,Gene Expression Regulation, Developmental ,Human brain ,Exons ,Middle Aged ,Gene expression profiling ,medicine.anatomical_structure ,Child, Preschool ,Female ,030217 neurology & neurosurgery - Abstract
Summary Here we report the generation and analysis of genome-wide exon-level transcriptome data from 16 brain regions comprising the cerebellar cortex, mediodorsal nucleus of the thalamus, striatum, amygdala, hippocampus, and 11 areas of the neocortex. The dataset was generated from 1,340 tissue samples collected from one or both hemispheres of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genotyping of 2.5 million SNPs and assessed copy number variations for all donors. Approximately 86% of protein-coding genes were found to be expressed using stringent criteria, and over 90% of these were differentially regulated at the whole transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occurred before birth, followed by an increase in the similarity among regional transcriptomes during postnatal lifespan. Genes were organized into functionally distinct co-expression networks, and sex differences were present in gene expression and exon usage. Finally, we demonstrate how these results can be used to profile trajectories of genes associated with neurodevelopmental processes, cell types, neurotransmitter systems, autism, and schizophrenia, as well as to discover associations between SNPs and spatiotemporal gene expression. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.
- Published
- 2011