TY - JOUR
T1 - An atlas of gene regulatory elements in adult mouse cerebrum
AU - Li, Yang Eric
AU - Preissl, Sebastian
AU - Hou, Xiaomeng
AU - Zhang, Ziyang
AU - Zhang, Kai
AU - Qiu, Yunjiang
AU - Poirion, Olivier B.
AU - Li, Bin
AU - Chiou, Joshua
AU - Liu, Hanqing
AU - Pinto-Duarte, Antonio
AU - Kubo, Naoki
AU - Yang, Xiaoyu
AU - Fang, Rongxin
AU - Wang, Xinxin
AU - Han, Jee Yun
AU - Lucero, Jacinta
AU - Yan, Yiming
AU - Miller, Michael
AU - Kuan, Samantha
AU - Gorkin, David
AU - Gaulton, Kyle J.
AU - Shen, Yin
AU - Nunn, Michael
AU - Mukamel, Eran A.
AU - Behrens, M. Margarita
AU - Ecker, Joseph R.
AU - Ren, Bing
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/10/7
Y1 - 2021/10/7
N2 - The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2–6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.
AB - The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2–6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.
UR - http://www.scopus.com/inward/record.url?scp=85116419373&partnerID=8YFLogxK
U2 - 10.1038/s41586-021-03604-1
DO - 10.1038/s41586-021-03604-1
M3 - Article
C2 - 34616068
AN - SCOPUS:85116419373
SN - 0028-0836
VL - 598
SP - 129
EP - 136
JO - Nature
JF - Nature
IS - 7879
ER -