A spatial multi-omics atlas of immunosenescence reveals germinal-center B cell alteration in human lymph nodes
Year: 2026
Type: article
Study design: Observational Study
Abstract: Immunosenescence is a hallmark of human aging and contributes to age-related immune decline, yet the development of senescence-associated phenotypes in the human lymphoid organs remains poorly understood. Here, we integrate single-cell and spatial multi-omics to systematically characterize age-related senescence in human lymph nodes (LNs) across the lifespan. Spatial proteomic profiling of 99 LN sections from 51 donors (18–86 years) using high-plex immunofluorescence (∼20 million cells) mapped senescence markers (p16, p21, HMGB1, and γ-H2AX) at single-cell resolution, revealing diverse senescent-like cell types ("senotypes") and a stepwise shift from extrafollicular to germinal-center localization with age. In aged LNs, germinal-center B cells exhibit focal accumulation of senescence-associated programs, accompanied by impaired functional signatures, metabolic remodeling, and altered regulatory networks. These findings define a spatially organized landscape of immunosenescence in human lymphoid tissue and highlight germinal-center B cells as a key locus of age-associated immune dysfunction.
Source: Cell Press Blue
Authors: Negin Farzad, Archibald Enninful, Yao Lu, Fabio Parisi, Anthony A. Fung, Yumi Kwon, Yajuan Li, Margaux Labrosse, Mingyu Yang, Francesco Strino, Liang Chen, Junchen Yang, Mei Zhong, Fu Gao, Bo Tao, Joseph Cunningham, Zhiliang Bai, Haikuo Li, Fang Wang, Michael Stankewich, Dongjoo Kim, Mingze Dong, Lisa M. Bramer, Keyi Li, Meera R. Bhat, Evan J. Loe, Joseph Craft, Ljiljana Pasa-Tolic, Stephanie Halene, Lingyan Shi, Yuval Kluger, Mina L. Xu, Rong Fan
Institutions: University of Wisconsin–Madison, Yale University, Pacific Northwest National Laboratory, Environmental Molecular Sciences Laboratory, University of California San Diego, Centre National de la Recherche Scientifique, Inserm, École Nationale Vétérinaire de Toulouse, RESTORE, Université de Toulouse, Johns Hopkins University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1142427047, High-spatial-resolution ECM-inclusive multi-omics sequencing of human PFA and FFPE tissue slides, Center for Human Lymphoma Spatiotemporal Atlas (HuLymSTA), Ex vivo analysis of human brain tumor cells in a microvascular niche model, Highly scalable and sensitive spatial transcriptomic and epigenomic sequencing of brain tissues from human and non-human primate, Yale TMC for Cellular Senescence in Lymphoid Organs, Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics), High-throughput in vivo and in vitro functional and multi-omics screens of neuropsychiatric and neurodevelopmental disorder risk genes, Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
OpenAlex ID: W7163900359