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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum

Yang Eric Li, View ORCID ProfileSebastian Preissl, Xiaomeng Hou, Ziyang Zhang, View ORCID ProfileKai Zhang, View ORCID ProfileRongxin Fang, View ORCID ProfileYunjiang Qiu, View ORCID ProfileOlivier Poirion, View ORCID ProfileBin Li, View ORCID ProfileHanqing Liu, View ORCID ProfileXinxin Wang, View ORCID ProfileJee Yun Han, View ORCID ProfileJacinta Lucero, View ORCID ProfileYiming Yan, View ORCID ProfileSamantha Kuan, View ORCID ProfileDavid Gorkin, View ORCID ProfileMichael Nunn, View ORCID ProfileEran A. Mukamel, M. Margarita Behrens, Joseph Ecker, View ORCID ProfileBing Ren
doi: https://doi.org/10.1101/2020.05.10.087585
Yang Eric Li
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Sebastian Preissl
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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  • ORCID record for Sebastian Preissl
Xiaomeng Hou
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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Ziyang Zhang
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Kai Zhang
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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  • ORCID record for Kai Zhang
Rongxin Fang
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Yunjiang Qiu
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Olivier Poirion
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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Bin Li
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Hanqing Liu
3Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA
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Xinxin Wang
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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Jee Yun Han
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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Jacinta Lucero
4Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Yiming Yan
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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Samantha Kuan
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
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David Gorkin
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
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Michael Nunn
3Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA
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Eran A. Mukamel
5Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA
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M. Margarita Behrens
4Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
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Joseph Ecker
3Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA
6Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, 92037, USA
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Bing Ren
1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093, USA
2Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, School of Medicine, La Jolla, CA, USA
7Institute of Genomic Medicine, Moores Cancer Center, University of California San Diego, School of Medicine, La Jolla, CA, USA
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  • For correspondence: biren@ucsd.edu
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ABSTRACT

The mammalian cerebrum performs high level sensory, motor control and cognitive functions through highly specialized cortical networks and subcortical nuclei. Recent surveys of mouse and human brains with single cell transcriptomics1–3 and high-throughput imaging technologies4,5 have uncovered hundreds of neuronal cell types and a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each brain cell type have yet to be elucidated. Here, we probe the accessible chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to define 491,818 candidate cis regulatory DNA elements in 160 distinct sub-types. We link a significant fraction of them to putative target genes expressed in diverse cerebral cell types and uncover transcriptional regulators 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 non-coding risk variants associated with various neurological disease and traits in humans. To facilitate the dissemination of information, we have set up a web portal (http://catlas.org/mousebrain).

Competing Interest Statement

B.R. is a co-founder and consultant of Arima Genomics, Inc.. J.R.E is on the scientific advisory board of Zymo Research, Inc

Footnotes

  • Add middle name for Yang Li; Capitalize name of Ziyang Zhang. Fixed a typo in the main text.

  • http://catlas.org/mousebrain

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum
Yang Eric Li, Sebastian Preissl, Xiaomeng Hou, Ziyang Zhang, Kai Zhang, Rongxin Fang, Yunjiang Qiu, Olivier Poirion, Bin Li, Hanqing Liu, Xinxin Wang, Jee Yun Han, Jacinta Lucero, Yiming Yan, Samantha Kuan, David Gorkin, Michael Nunn, Eran A. Mukamel, M. Margarita Behrens, Joseph Ecker, Bing Ren
bioRxiv 2020.05.10.087585; doi: https://doi.org/10.1101/2020.05.10.087585
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An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum
Yang Eric Li, Sebastian Preissl, Xiaomeng Hou, Ziyang Zhang, Kai Zhang, Rongxin Fang, Yunjiang Qiu, Olivier Poirion, Bin Li, Hanqing Liu, Xinxin Wang, Jee Yun Han, Jacinta Lucero, Yiming Yan, Samantha Kuan, David Gorkin, Michael Nunn, Eran A. Mukamel, M. Margarita Behrens, Joseph Ecker, Bing Ren
bioRxiv 2020.05.10.087585; doi: https://doi.org/10.1101/2020.05.10.087585

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