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Series GSE25219 Query DataSets for GSE25219
Status Public on Oct 27, 2011
Title Spatio-temporal transcriptome of the human brain
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The development of the human brain is a complex and precisely regulated process that unfolds over a protracted period of time. Human-specific features of this process, especially the ways in which highly complex neural circuits of the cerebral cortex form, are likely to be important factors in the evolution of human specializations. However, in addition to giving us remarkable cognitive and motor abilities, the formation of intricate neural circuits may have also increased our susceptibility to psychiatric and neurodegenerative disorders. Furthermore, substantial evidence suggests that the symptoms and progression of many brain disorders are dramatically influenced by genetic and developmental processes that define regional cell phenotypes and connectivity. Sex differences also play an important role in brain development and function and are a risk factor for several brain disorders, such as autism spectrum disorders (ASD) and depression. Thus understanding the spatiotemporal dynamics and functional organization of the brain transcriptome is essential to teasing out the keys to human neurodevelopment, sexual dimorphism, and evolution as well as our increased susceptibility to certain brain disorders. Most transcriptome studies of the developing brain have been restricted to rodents, and those performed in humans and nonhuman primates have included relatively small sample sizes and predominantly focused on few regions or developmental time points. Because many prominent features of human brain development significantly diverge from those of well-characterized model organisms, the translation of knowledge across species is difficult, and it is likely that many underlying genetic processes have gone undetected. In this study, we have taken a genome-wide approach to analyze the human transcriptome at single-exon resolution with ~1.4 million exon-level probe sets in 16 brain regions from donors representing both sexes and multiple ethnicities, across pre and postnatal development, including adolescence, and adulthood. We also generated genome-wide genotype data for 2.5 million single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for each specimen. Our analyses of the data revealed several features of the human brain transcriptome: spatiotemporal expression dynamics of individual and functionally related groups of genes, differential exon usage, sex-specific expression patterns and exon usage, and organization of the transcriptome into functional modules. We also profiled developmental trajectories of genes important for neurobiological themes and genes associated with ASD and schizophrenia. Finally, we present associations between specific SNPs and gene expression levels in different brain regions across development. The dataset presented here provides research opportunities and a wealth of information not previously available to the scientific community.
 
Overall design 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 samples collected from 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 genome-wide genotyping of 2.5 million single nucleotide polymorphisms (SNPs) and assessed copy number variations for all donors. We found that approximately 86% of protein-coding genes are expressed above background, and over 90% of these are differentially regulated at the whole transcript or exon level across regions and/or time. The majority of these spatiotemporal differences occur before birth, followed by a progressive increase in the similarity among regional transcriptome during the postnatal lifespan. Distinctive transcriptional patterns were also identified among neocortical areas, including an alternative isoform of ANKRD32 that is transiently upregulated in the late midfetal frontal cortex of human but not mouse. Developmentally and regionally regulated differences in gene expression and exon usage were also identified between males and females, including IGF2, an imprinted gene implicated in brain growth and cognitive function, and NLGN4X, a candidate gene for autism spectrum disorders. We found that the developing transcriptome is organized into functionally distinct large-scale networks of co-regulated transcripts. We also observed marked differences in expression trajectories of genes associated with specific neurodevelopmental processes, neural cell types, neurotransmitter systems, autism spectrum disorders, and schizophrenia. Association analysis of the SNP genotypes and transcriptome revealed potential polymorphic regulators of gene expression in different regions across development. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of brain development and evolution.

This submission represents the transcriptome component of the study.
Submitter did not submit SNP and CNV data due to privacy issue of patients.
 
Contributor(s) Kang H, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N
Citation(s) 22031440, 26428952
Submission date Nov 09, 2010
Last update date Feb 18, 2019
Contact name Feng Cheng
E-mail feng.cheng@yale.edu
Phone 2037855941
Organization name Yale University
Department Neurobiology
Lab Prof. Nenad Sestan
Street address 333 Cedar Street SHM C338
City New Haven
State/province CT
ZIP/Postal code 06511
Country USA
 
Platforms (2)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
GPL5188 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version]
Samples (2680)
GSM703914 HSB92_A1C_R [gene-level]
GSM703915 HSB92_AMY_R [gene-level]
GSM703916 HSB92_CBC_R [gene-level]
Relations
BioProject PRJNA134455

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25219.pdf.gz 3.5 Mb (ftp)(http) PDF
GSE25219_DABG_pvalue.csv.gz 12.6 Mb (ftp)(http) CSV
GSE25219_RAW.tar 64.2 Gb (http)(custom) TAR (of CEL)
GSE25219_abbreviation.pdf.gz 116.8 Kb (ftp)(http) PDF
Raw data provided as supplementary file
Processed data included within Sample table

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