A comparative atlas of single-cell chromatin accessibility in the human brain-Reference-Cited by-同舟云学术

A comparative atlas of single-cell chromatin accessibility in the human brain

Published:2023-10-13 Issue:6667 Volume:382 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Li Yang Eric¹^ORCID,Preissl Sebastian²^ORCID,Miller Michael²^ORCID,Johnson Nicholas D.³^ORCID,Wang Zihan⁴^ORCID,Jiao Henry²,Zhu Chenxu¹,Wang Zhaoning¹^ORCID,Xie Yang¹^ORCID,Poirion Olivier²^ORCID,Kern Colin²^ORCID,Pinto-Duarte Antonio³^ORCID,Tian Wei³^ORCID,Siletti Kimberly⁵^ORCID,Emerson Nora³^ORCID,Osteen Julia³,Lucero Jacinta³,Lin Lin²,Yang Qian²,Zhu Quan²,Zemke Nathan²^ORCID,Espinoza Sarah²^ORCID,Yanny Anna Marie⁶,Nyhus Julie⁶^ORCID,Dee Nick⁶^ORCID,Casper Tamara⁶^ORCID,Shapovalova Nadiya⁶^ORCID,Hirschstein Daniel⁶,Hodge Rebecca D.⁶^ORCID,Linnarsson Sten⁵^ORCID,Bakken Trygve⁶^ORCID,Levi Boaz⁶^ORCID,Keene C. Dirk⁷^ORCID,Shang Jingbo⁴^ORCID,Lein Ed⁶^ORCID,Wang Allen²^ORCID,Behrens M. Margarita³^ORCID,Ecker Joseph R.³⁸^ORCID,Ren Bing¹²^ORCID

Affiliation:

1. Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

2. Center for Epigenomics, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA.

3. The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

4. Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.

5. Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.

6. Allen Institute for Brain Science, Seattle, WA 98109, USA.

7. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98104, USA.

8. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

Abstract

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer’s disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adf7044

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