Human body single-cell atlas of three-dimensional genome organization and DNA methylation
- Jingtian Zhou
- Yue Wu
- Hanqing Liu
- Wei Tian
- Rosa G. Castanon
- Anna Bartlett
- Zuolong Zhang
- Guocong Yao
- Dengxiaoyu Shi
- Ben Clock
- Samantha Marcotte
- Joseph R. Nery
- Michelle Liem
- Naomi Claffey
- Lara Boggeman
- Cesar Barragan
- Rafael Arrojo e Drigo
- Annika K. Weimer
- Minyi Shi
- Johnathan Cooper-Knock
- Sai Zhang
- Michael P. Snyder
- Sebastian Preissl
- Bing Ren
- Carolyn O’Connor
- Shengbo Chen
- Chongyuan Luo
- Jesse R. Dixon
- Joseph R. Ecker
2026-07-23
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.