Transcriptional landscape of the prenatal human brain.
The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.
1] Allen Institute for Brain Science, Seattle, Washington 98103, USA [2].
Jeremy A
JA
Miller
1] Allen Institute for Brain Science, Seattle, Washington 98103, USA [2].
Song-Lin
SL
Ding
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Susan M
SM
Sunkin
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Kimberly A
KA
Smith
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Lydia
L
Ng
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Aaron
A
Szafer
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Amanda
A
Ebbert
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Zackery L
ZL
Riley
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Joshua J
JJ
Royall
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Kaylynn
K
Aiona
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
James M
JM
Arnold
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Crissa
C
Bennet
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Darren
D
Bertagnolli
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Krissy
K
Brouner
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Stephanie
S
Butler
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Shiella
S
Caldejon
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Anita
A
Carey
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Christine
C
Cuhaciyan
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Rachel A
RA
Dalley
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Nick
N
Dee
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Tim A
TA
Dolbeare
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Benjamin A C
BA
Facer
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
David
D
Feng
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Tim P
TP
Fliss
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Garrett
G
Gee
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Jeff
J
Goldy
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Lindsey
L
Gourley
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Benjamin W
BW
Gregor
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Guangyu
G
Gu
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Robert E
RE
Howard
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Jayson M
JM
Jochim
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Chihchau L
CL
Kuan
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Christopher
C
Lau
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Chang-Kyu
CK
Lee
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Felix
F
Lee
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Tracy A
TA
Lemon
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Phil
P
Lesnar
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Bergen
B
McMurray
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Naveed
N
Mastan
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Nerick
N
Mosqueda
Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA.
Theresa
T
Naluai-Cecchini
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Nhan-Kiet
NK
Ngo
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Julie
J
Nyhus
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Aaron
A
Oldre
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Eric
E
Olson
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Jody
J
Parente
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Patrick D
PD
Parker
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Sheana E
SE
Parry
1] Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA.
Allison
A
Stevens
Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Mihovil
M
Pletikos
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Melissa
M
Reding
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Kate
K
Roll
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
David
D
Sandman
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Melaine
M
Sarreal
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Sheila
S
Shapouri
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Nadiya V
NV
Shapovalova
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Elaine H
EH
Shen
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Nathan
N
Sjoquist
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Clifford R
CR
Slaughterbeck
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Michael
M
Smith
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Andy J
AJ
Sodt
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Derric
D
Williams
Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Lilla
L
Zöllei
1] Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA.
Bruce
B
Fischl
1] Program in Computational Biology and Bioinformatics, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA [2] Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA.
Mark B
MB
Gerstein
Program in Neurogenetics, Department of Neurology and Semel Institute David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
Daniel H
DH
Geschwind
Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA.
Ian A
IA
Glass
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Michael J
MJ
Hawrylycz
1] Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA [2] Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98105, USA.
Robert F
RF
Hevner
Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
Hao
H
Huang
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Allan R
AR
Jones
Zilkha Neurogenetic Institute, and Department of Psychiatry, University of Southern California, Los Angeles, California 90033, USA.
James A
JA
Knowles
1] Department of Pediatrics, Children's Hospital, Los Angeles, California 90027, USA [2] Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
Pat
P
Levitt
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
John W
JW
Phillips
Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Nenad
N
Sestan
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Paul
P
Wohnoutka
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Chinh
C
Dang
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Amy
A
Bernard
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
John G
JG
Hohmann
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
Ed S
ES
Lein
D000716:Anatomy, Artistic; D000818:Animals; D001271:Atlases as Topic; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D051379:Mice; D019579:Neocortex / Q000196:embryology / Q000378:metabolism; D013045:Species Specificity; D059467:Transcriptome