Human body single-cell atlas of three-dimensional genome organization and DNA methylation
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.
Authors
- Chongyuan Luo (ORCID: https://orcid.org/0000-0002-8541-0695)
- Sebastian Preißl (ORCID: https://orcid.org/0000-0001-8971-5616)
- Michael Snyder (ORCID: https://orcid.org/0000-0003-0784-7987)
- Naomi Claffey
- Joseph R. Ecker (ORCID: https://orcid.org/0000-0001-5799-5895)
- Lara Boggeman
- Anna Bartlett (ORCID: https://orcid.org/0000-0001-7059-4033)
- Samantha Marcotte (ORCID: https://orcid.org/0000-0003-0309-2628)
- Johnathan Cooper‐Knock (ORCID: https://orcid.org/0000-0002-0873-8689)
- Carolyn O’Connor (ORCID: https://orcid.org/0000-0002-3301-7912)
- Rosa Castanon (ORCID: https://orcid.org/0000-0003-1791-002X)
- Michelle Liem (ORCID: https://orcid.org/0009-0004-0542-7166)
- Ben Clock (ORCID: https://orcid.org/0000-0003-2968-0727)
- Rafael Arrojo e Drigo (ORCID: https://orcid.org/0000-0001-7712-013X)
- Hanqing Liu (ORCID: https://orcid.org/0000-0002-5114-6048)
- Shengbo Chen (ORCID: https://orcid.org/0000-0002-9026-8128)
- S Bingrong Zhang
- Jingtian Zhou (ORCID: https://orcid.org/0000-0003-2060-1922)
- Jesse R. Dixon (ORCID: https://orcid.org/0000-0002-6273-2181)
- Bing Ren (ORCID: https://orcid.org/0000-0002-5435-1127)
- Wei Tian (ORCID: https://orcid.org/0000-0002-2146-1717)
- Joseph R. Nery (ORCID: https://orcid.org/0000-0003-0153-5659)
- Yue Wu (ORCID: https://orcid.org/0009-0004-2428-0905)
- Zuolong Zhang (ORCID: https://orcid.org/0009-0009-2119-6464)
- Difang Shi
- Minyi Shi (ORCID: https://orcid.org/0000-0003-1616-8353)
- Cesar Barragan (ORCID: https://orcid.org/0000-0002-7897-8215)
- Guocong Yao (ORCID: https://orcid.org/0009-0007-3839-0728)
- Annika K. Weimer
Institutions
- Broad Institute (US)
- Salk Institute for Biological Studies (US)
- Howard Hughes Medical Institute (US)
- Nanchang University (CN)
- University of Graz (AT)
- University of Freiburg (DE)
- University of California, Los Angeles (US)
- Henan University (CN)
- Vanderbilt University (US)
- Harvard University Press (US)
- Foundation Center (US)
- Yale University (US)
- University of Florida (US)
- University of California San Diego (US)
- Novo Nordisk (United States) (US)
- Palo Alto Institute (US)
- Stanford Medicine (US)
- Arc Research Institute
- Vanderbilt University Medical Center (US)
- University of Sheffield (GB)
Publication Details
- Journal
- Science
- Published
- 2026-07-23
- DOI
- https://doi.org/10.1126/science.adx0673
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- National Human Genome Research Institute
- NIH Office of the Director
- National Cancer Institute