{ "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.", "abstract_shown": true, "affiliations": [ "Arc Institute, Palo Alto, CA, USA", "Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, USA", "Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA", "Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA", "Society of Fellows, Harvard University, Cambridge, MA, USA", "School of Software, Henan University, Kaifeng, Henan, China", "School of Computer and Information Engineering, Henan University, Kaifeng, Henan, China", "Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA", "Flow Cytometry Core Facility, Salk Institute for Biological Studies, La Jolla, CA, USA", "Center for Computational Systems Biology, Vanderbilt University, Nashville, TN, USA", "Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA", "Diabetes Research and Training Center (DRTC), Vanderbilt University Medical Center, Nashville, TN, USA", "Department of Genetics, Stanford School of Medicine, Stanford, CA, USA", "Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA", "Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK", "Department of Biomedical Informatics & Data Science, Yale School of Medicine, New Haven, CT, USA", "Department of Epidemiology, University of Florida, Gainesville, FL, USA", "Center for Epigenomics, University of California San Diego, La Jolla, CA, USA", "Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria", "Field of Excellence BioHealth, University of Graz, Graz, Austria", "Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany", "Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA", "School of Software, Nanchang University, Nanchang, Jiangxi, China", "Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA", "Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA, USA" ], "article_type": null, "arxiv": null, "author_total": 29, "authors": [ { "affs": [ 0, 1, 2 ], "name": "Jingtian Zhou", "orcid": "0000-0003-2060-1922" }, { "affs": [ 3, 2 ], "name": "Yue Wu", "orcid": "0009-0004-2428-0905" }, { "affs": [ 2, 4 ], "name": "Hanqing Liu", "orcid": "0000-0002-5114-6048" }, { "affs": [ 2 ], "name": "Wei Tian", "orcid": "0000-0002-2146-1717" }, { "affs": [ 2 ], "name": "Rosa Castanon", "orcid": "0000-0003-1791-002X" }, { "affs": [ 2 ], "name": "Anna Bartlett", "orcid": "0000-0001-7059-4033" }, { "affs": [ 5 ], "name": "Zuolong Zhang", "orcid": "0009-0009-2119-6464" }, { "affs": [ 6 ], "name": "Guocong Yao", "orcid": "0009-0007-3839-0728" }, { "affs": [ 2 ], "name": "Difang Shi", "orcid": "0000-0001-6373-7198" }, { "affs": [ 7 ], "name": "Ben Clock", "orcid": "0000-0003-2968-0727" }, { "affs": [ 7 ], "name": "Samantha Marcotte", "orcid": "0000-0003-0309-2628" }, { "affs": [ 2 ], "name": "Joseph R. Nery", "orcid": "0000-0003-0153-5659" }, { "affs": [ 8 ], "name": "Michelle Liem", "orcid": "0009-0004-0542-7166" }, { "affs": [ 8 ], "name": "Naomi Claffey" }, { "affs": [ 8 ], "name": "Lara Boggeman" }, { "affs": [ 2 ], "name": "Cesar Barragan", "orcid": "0000-0002-7897-8215" }, { "affs": [ 9, 10, 11 ], "name": "Rafael Arrojo e Drigo", "orcid": "0000-0001-7712-013X" }, { "affs": [ 12, 13 ], "name": "Annika K K Weimer", "orcid": "0000-0001-9944-8769" }, { "affs": [ 12 ], "name": "Minyi Shi", "orcid": "0009-0004-3266-6824" }, { "affs": [ 14 ], "name": "Johnathan Cooper‐Knock", "orcid": "0000-0002-0873-8689" }, { "affs": [ 15, 16 ], "name": "Sai Zhang", "orcid": "0000-0001-5996-6086" }, { "affs": [ 12 ], "name": "Michael P. Snyder", "orcid": "0000-0003-0784-7987" }, { "affs": [ 17, 18, 19, 20 ], "name": "Sebastian Preißl", "orcid": "0000-0001-8971-5616" }, { "affs": [ 17, 21 ], "name": "Bing Ren", "orcid": "0000-0002-5435-1127" }, { "affs": [ 8 ], "name": "Carolyn O’Connor", "orcid": "0000-0002-3301-7912" }, { "affs": [ 22 ], "name": "Shengbo Chen", "orcid": "0000-0002-9026-8128" }, { "affs": [ 23 ], "name": "Chongyuan Luo", "orcid": "0000-0002-8541-0695" }, { "affs": [ 7 ], "name": "Jesse R. Dixon", "orcid": "0000-0002-6273-2181" }, { "affs": [ 2, 24 ], "name": "Joseph R. Ecker", "orcid": "0000-0001-5799-5895" } ], "bibtex": "https://research.draconitic.com/paper/86ekbxy1m5ewj.bib", "cited_by": 22, "doi": "10.1126/science.adx0673", "fulltext_url": null, "id": "86ekbxy1m5ewj", "issns": [ "0036-8075", "0193-4511", "1095-9203" ], "landing_url": "https://doi.org/10.1126/science.adx0673", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1312|Genomics and Chromatin Dynamics" ] ], "openalex": "W7170166607", "pdf_url": null, "pmcid": "PMC13409364", "pmid": "42490476", "published": "2026-07-23", "publisher": "American Association for the Advancement of Science", "ris": "https://research.draconitic.com/paper/86ekbxy1m5ewj.ris", "sources": [ { "first_seen": "2026-10-30T13:26:48Z", "native_id": "W7170166607", "source": "openalex", "url": "https://doi.org/10.1126/science.adx0673" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Genomics and Chromatin Dynamics", "subfield": "molecular-biology" } ], "title": "Human body single-cell atlas of three-dimensional genome organization and DNA methylation", "title_text": "Human body single-cell atlas of three-dimensional genome organization and DNA methylation", "type": "peer-reviewed", "updated_at": "2026-11-09T13:21:05Z", "url": "https://research.draconitic.com/paper/86ekbxy1m5ewj", "venue": "Science", "versions": [] }