Human body single-cell atlas of three-dimensional genome organization and DNA methylation

• 成果类型: Article
• 署名作者: Zhou, Jingtian; Wu, Yue; Liu, Hanqing; Tian, Wei; Castanon, Rosa G.; Bartlett, Anna; Zhang, Zuolong; Yao, Guocong; Shi, Dengxiaoyu; Clock, Ben; Marcotte, Samantha; Nery, Joseph R.; Liem, Michelle; Claffey, Naomi; Boggeman, Lara; Barragan, Cesar; Arrojo e Drigo, Rafael; Weimer, Annika K.; Shi, Minyi; Cooper-Knock, Johnathan; Zhang, Sai; Snyder, Michael P.; Preissl, Sebastian; Ren, Bing; O'Connor, Carolyn; Chen, Shengbo; Luo, Chongyuan; Dixon, Jesse R.; Ecker, Joseph R.
• 署名单位: Salk Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Harvard University; Henan University; Henan University; Salk Institute; Salk Institute; Vanderbilt University; Vanderbilt University; Vanderbilt University; Stanford University; Stanford Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Sheffield; Yale University; State University System of Florida; University of Florida; University of California System; University of California San Diego; University of Freiburg; University of Graz; University of Graz; University of California System; University of California San Diego; Nanchang University; University of California System; University of California Los Angeles; David Geffen School of Medicine at UCLA; Salk Institute; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adx0673
• 发表日期: 2026-07-23
• 页码: eadx0673
• 关键词: chromatin accessibility; transcription factors; regulatory elements; REVEALS PRINCIPLES; hi-c; rna; differentiation; architecture; diversity; domains

摘要

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.