Human body single-cell atlas of three-dimensional genome organization and DNA methylation
Abstract
Higher-order chromatin structure and DNA methylation are critical for gene regulation, but how these vary across the human body remains unclear. We performed multiomic profiling of three-dimensional (3D) genome structure and DNA methylation for 86,689 single nuclei across 16 tissues, identifying 35 major and 206 cell subtypes. We revealed extensive changes in CG and non-CG methylation across cell types and characterized 3D chromatin structure at an unprecedented cellular resolution. Extensive discrepancies exist between cell types delineated by DNA methylation and genome structure, which indicates that the role of distinct epigenomic features in maintaining cell identity may vary by lineage. This study expands our understanding of the diversity of DNA methylation and chromatin structure and offers a reference for exploring gene regulation in human health and disease.
Article Details
Journal Info
Science
American Association for the Advancement of Science
Authors (29)
Jingtian Zhou
Yue Wu
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Hanqing Liu
Wei Tian
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Rosa G. Castanon
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Anna Bartlett
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Zuolong Zhang
School of Software, Henan University, Kaifeng, Henan, China.
Guocong Yao
School of Computer and Information Engineering, Henan University, Kaifeng, Henan, China.
Dengxiaoyu Shi
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Ben Clock
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Samantha Marcotte
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Joseph R. Nery
Michelle Liem
Flow Cytometry Core Facility, Salk Institute for Biological Studies, La Jolla, CA, USA.
Naomi Claffey
Flow Cytometry Core Facility, Salk Institute for Biological Studies, La Jolla, CA, USA.
Lara Boggeman
Flow Cytometry Core Facility, Salk Institute for Biological Studies, La Jolla, CA, USA.
Cesar Barragan
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Rafael Arrojo e Drigo
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Annika K. Weimer
Minyi Shi
Department of Genetics, Stanford School of Medicine, Stanford, CA, USA.
Johnathan Cooper-Knock
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Sai Zhang
Department of Biomedical Informatics & Data Science, Yale School of Medicine, New Haven, CT, USA.
Michael P. Snyder
Sebastian Preissl
Center for Epigenomics, University of California San Diego, La Jolla, CA, USA.
Bing Ren
Carolyn O’Connor
Flow Cytometry Core Facility, Salk Institute for Biological Studies, La Jolla, CA, USA.
Shengbo Chen
School of Software, Nanchang University, Nanchang, Jiangxi, China.
Chongyuan Luo
Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Jesse R. Dixon
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Joseph R. Ecker