A 3D genome atlas of human tonsil and the role of loop extrusion in B cell somatic hypermutation

• 成果类型: Article
• 署名作者: Cheng, Yubao; Wang, Jianshu; Zhang, Yuan; Yadavalli, Anurupa Devi; Liu, Miao; Jin, Shengyan; Buddle, Grace; Haberman, Ann; Schatz, David G.; Wang, Siyuan
• 署名单位: Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale New Haven Hospital.
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adw4243
• 发表日期: 2026-07-23
• 页码: eadw4243
• 关键词: molecular-mechanisms; spatial-organization; HUMAN-CHROMOSOMES; germinal-centers; super-enhancers; TARGETS AID; transcription; architecture; translocations; susceptibility

摘要

B cell maturation within the germinal center tissue microenvironment involves immunoglobulin gene diversification by somatic hypermutation (SHM). How three-dimensional (3D) genome architecture influences SHM is not fully understood. We leveraged sequencing-based and image-based 3D genomics and transcriptomics to map single-cell 3D genome organization and gene expression across cell types and states in human tonsils and in B cell lymphoma cell lines. These analyses revealed trajectories of compartment, looping, and nuclear position changes during the B cell immune response and activation of SHM. Targeted protein degradation of cohesin component RAD21 revealed its contribution to enabling SHM. Our results provide a single-cell 3D genome atlas of human tonsil cells and outline the links between the chromatin loop extrusion machinery and SHM.