Single-cell DNA methylation and 3D genome architecture in the human brain-Reference-Cited by-同舟云学术

Single-cell DNA methylation and 3D genome architecture 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:

Tian Wei¹^ORCID,Zhou Jingtian¹²^ORCID,Bartlett Anna¹^ORCID,Zeng Qiurui¹³,Liu Hanqing¹^ORCID,Castanon Rosa G.¹^ORCID,Kenworthy Mia¹^ORCID,Altshul Jordan¹^ORCID,Valadon Cynthia¹^ORCID,Aldridge Andrew¹^ORCID,Nery Joseph R.¹^ORCID,Chen Huaming¹^ORCID,Xu Jiaying¹^ORCID,Johnson Nicholas D.⁴^ORCID,Lucero Jacinta⁴,Osteen Julia K.⁴,Emerson Nora⁴^ORCID,Rink Jon⁴^ORCID,Lee Jasper⁴^ORCID,Li Yang E.⁵^ORCID,Siletti Kimberly⁶^ORCID,Liem Michelle⁷^ORCID,Claffey Naomi⁷,O’Connor Carolyn⁷^ORCID,Yanny Anna Marie⁸,Nyhus Julie⁸^ORCID,Dee Nick⁸^ORCID,Casper Tamara⁸^ORCID,Shapovalova Nadiya⁸^ORCID,Hirschstein Daniel⁸,Ding Song-Lin⁸^ORCID,Hodge Rebecca⁸^ORCID,Levi Boaz P.⁸^ORCID,Keene C. Dirk⁹^ORCID,Linnarsson Sten⁶^ORCID,Lein Ed⁸^ORCID,Ren Bing⁵¹⁰¹¹¹²¹³^ORCID,Behrens M. Margarita⁴^ORCID,Ecker Joseph R.¹¹⁴^ORCID

Affiliation:

1. Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

2. Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92037, USA.

3. Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92037, USA.

4. Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

5. Ludwig Institute for Cancer Research, La Jolla, CA 92037, USA.

6. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

7. Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

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

9. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.

10. Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.

11. Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.

12. Institute of Genomic Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.

13. Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.

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

Abstract

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. We further developed single-cell methylation barcodes that reliably predict brain cell types using the methylation status of select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell-type–specific gene regulation in adult human brains.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adf5357

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