Human Lymph Node Cellular Senescence Atlas Reveals Age-Dependent Alteration in Germinal Center B Cell Function and Niches
-H2AX) at single-cell resolution, revealing diverse senescent-like cell types ("senotypes") and a stepwise shift from extrafollicular to germinal center (GC) localization with age. Notably, we observed focal clonal-like senescence in GC B cells in older donor LNs. Spatial transcriptomics, epigenomics, and metabolic imaging of selected samples further elucidate the multi-omics signatures and underlying mechanisms of functional impairment, metabolic remodeling, and distinct regulatory programs in senescent-like GC B cells. This study presents a comprehensive spatial atlas of senescence-associated immune states in human lymph nodes, revealing cell-type-specific and spatial heterogeneity that may contribute to immunosenescence and the decline of immune function during aging.
Authors
- Negin Farzad (ORCID: https://orcid.org/0009-0002-5391-9363)
- Haikuo Li (ORCID: https://orcid.org/0000-0003-3697-5662)
- Zhiliang Bai (ORCID: https://orcid.org/0000-0002-3977-3057)
- Archibald Enninful (ORCID: https://orcid.org/0000-0002-6350-6530)
- Anthony A. Fung (ORCID: https://orcid.org/0000-0003-1631-7451)
- Lisa Bramer (ORCID: https://orcid.org/0000-0002-8384-1926)
- Francesco Strino (ORCID: https://orcid.org/0000-0002-9310-4794)
- Michael C. Stankewich
- Margaux Labrosse (ORCID: https://orcid.org/0000-0001-5209-7973)
- Mingyu Yang (ORCID: https://orcid.org/0000-0003-0986-3825)
- Fabio Parisi
- Meera Bhat
- Yumi Kwon
- Rong Fan
- Fang Wang
- Fu Gao
- Yajuan Li
- Mingze Dong
- Liang Chen
- Mina L. Xu
- Mei Zhong
- Junchen Yang
- Dongjoo Kim
- Bo Tao
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- University of Wisconsin–Madison (US)
- Pacific Northwest National Laboratory (US)
- Johns Hopkins University (US)
- Inserm (FR)
- École Nationale Vétérinaire de Toulouse (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Environmental Molecular Sciences Laboratory (US)
- Yale University (US)
- La Jolla Bioengineering Institute (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-06
- DOI
- https://doi.org/10.64898/2026.04.02.716161
- Primary Topic
- Telomeres, Telomerase, and Senescence
- Type
- article
- Field-Weighted Citation Impact
- 0.00