Spatio-temporal transcriptome of the human brain.
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.
Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Hyo Jung
HJ
Kang
Yuka Imamura
YI
Kawasawa
Feng
F
Cheng
Ying
Y
Zhu
Xuming
X
Xu
Mingfeng
M
Li
André M M
AM
Sousa
Mihovil
M
Pletikos
Kyle A
KA
Meyer
Goran
G
Sedmak
Tobias
T
Guennel
Yurae
Y
Shin
Matthew B
MB
Johnson
Zeljka
Z
Krsnik
Simone
S
Mayer
Sofia
S
Fertuzinhos
Sheila
S
Umlauf
Steven N
SN
Lisgo
Alexander
A
Vortmeyer
Daniel R
DR
Weinberger
Shrikant
S
Mane
Thomas M
TM
Hyde
Anita
A
Huttner
Mark
M
Reimers
Joel E
JE
Kleinman
Nenad
N
Sestan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D040641:Quantitative Trait Loci / Q000235:genetics; D012727:Sex Characteristics; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult