Spatio-temporal transcriptome of the human brain

• Published in: Nature (London) Vol. 478; no. 7370; pp. 483 - 489
• Main Authors: Kang, Hyo Jung, Kawasawa, Yuka Imamura, Cheng, Feng, Zhu, Ying, Xu, Xuming, Li, Mingfeng, Sousa, André M. M., Pletikos, Mihovil, Meyer, Kyle A., Sedmak, Goran, Guennel, Tobias, Shin, Yurae, Johnson, Matthew B., Krsnik, Željka, Mayer, Simone, Fertuzinhos, Sofia, Umlauf, Sheila, Lisgo, Steven N., Vortmeyer, Alexander, Weinberger, Daniel R., Mane, Shrikant, Hyde, Thomas M., Huttner, Anita, Reimers, Mark, Kleinman, Joel E., Šestan, Nenad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.10.2011; Nature Publishing Group
• Subjects: 631/208/191/2018; 631/378/2571; 692/698/1688/1366/64; Adolescent; Adult; Aged; Aged, 80 and over; Aging - genetics; Biological and medical sciences; Brain; Brain - embryology; Brain - growth & development; Brain - metabolism; Child; Child, Preschool; Exons - genetics; Female; Fetus - metabolism; Fundamental and applied biological sciences. Psychology; Gender differences; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental - genetics; Gene Regulatory Networks - genetics; Genetic aspects; Genomes; Humanities and Social Sciences; Humans; Infant; Male; Middle Aged; Molecular and cellular biology; Molecular genetics; multidisciplinary; Nervous system diseases; Physiological aspects; Prenatal development; Quality Control; Quantitative Trait Loci - genetics; Science; Science (multidisciplinary); Sex Characteristics; Time Factors; Transcription. Transcription factor. Splicing. Rna processing; Transcriptome - genetics; Young Adult; United States; Human; Transcriptomics; Transcriptome; Encephalon
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature10523

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. Gene expression in the human brain Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-expression database from a variety of human brain samples ranging from before birth to over 80 years in age. Colantuoni et al . focus on the prefrontal cortex. Although they note significant expression pattern dynamics throughout development, they identify a consistent molecular architecture of transcription across subjects from different races despite the large number of genetic polymorphisms among them. Kang et al . produce a more comprehensive time course, exploring expression in 16 different brain areas, determining that the largest spatiotemporal variability occurs before birth, with transcriptomes in brain regions converging as we age.