An atlas of gene regulatory elements in adult mouse cerebrum
Yang Eric Li,
Sebastian Preissl,
Xiaomeng Hou,
Ziyang Zhang,
Kai Zhang,
Yunjiang Qiu,
Olivier B. Poirion,
Bin Li,
Joshua Chiou,
Hanqing Liu,
Antonio Pinto-Duarte,
Naoki Kubo,
Xiaoyu Yang,
Rongxin Fang,
Xinxin Wang,
Jee Yun Han,
Jacinta Lucero,
Yiming Yan,
Michael Miller,
Samantha Kuan,
David Gorkin,
Kyle J. Gaulton,
Yin Shen,
Michael Nunn,
Eran A. Mukamel,
M. Margarita Behrens,
Joseph R. Ecker and
Bing Ren ()
Additional contact information
Yang Eric Li: Ludwig Institute for Cancer Research
Sebastian Preissl: University of California San Diego, School of Medicine
Xiaomeng Hou: University of California San Diego, School of Medicine
Ziyang Zhang: Ludwig Institute for Cancer Research
Kai Zhang: Ludwig Institute for Cancer Research
Yunjiang Qiu: Ludwig Institute for Cancer Research
Olivier B. Poirion: University of California San Diego, School of Medicine
Bin Li: Ludwig Institute for Cancer Research
Joshua Chiou: University of California San Diego
Hanqing Liu: The Salk Institute for Biological Studies
Antonio Pinto-Duarte: Salk Institute for Biological Studies
Naoki Kubo: Ludwig Institute for Cancer Research
Xiaoyu Yang: University of California San Francisco
Rongxin Fang: Ludwig Institute for Cancer Research
Xinxin Wang: University of California San Diego, School of Medicine
Jee Yun Han: University of California San Diego, School of Medicine
Jacinta Lucero: Salk Institute for Biological Studies
Yiming Yan: Ludwig Institute for Cancer Research
Michael Miller: University of California San Diego, School of Medicine
Samantha Kuan: Ludwig Institute for Cancer Research
David Gorkin: University of California San Diego, School of Medicine
Kyle J. Gaulton: University of California San Diego
Yin Shen: University of California San Francisco
Michael Nunn: The Salk Institute for Biological Studies
Eran A. Mukamel: University of California, San Diego
M. Margarita Behrens: Salk Institute for Biological Studies
Joseph R. Ecker: The Salk Institute for Biological Studies
Bing Ren: Ludwig Institute for Cancer Research
Nature, 2021, vol. 598, issue 7879, 129-136
Abstract:
Abstract 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.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:598:y:2021:i:7879:d:10.1038_s41586-021-03604-1
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DOI: 10.1038/s41586-021-03604-1
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