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Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy-Induced Senescent Cells

文献类型：期刊论文

作者Zhang, Ge4; Zhang, Wei4; Wang, Changxu4; Jiang, Zhirui2,4; Xu, Qixia2,4; Li, Haipeng4; Kirkland, James L.1,3; Wei, Gang4,6; Sun, Yu2,4,5
刊名AGING CELL
出版日期2026
卷号25期号:1页码:21
ISSN号1474-9718
DOI10.1111/acel.70366
通讯作者Zhang, Ge(zhangge2018@sinh.ac.cn) ; Wei, Gang(gwei@siii.cas.cn) ; Sun, Yu(sunyu@sinh.ac.cn)
英文摘要Cellular senescence is a fundamental biological process contributing to aging, often accompanied by extensive chromatin remodeling. Dynamic alterations of three-dimensional (3D) genomic spatial structure, driven by chromatin reorganization, play a critical role in cell fate determination, but their relevance in therapy-induced senescence (TIS) remains underexplored. Here, we perform an integrative multi-omics analysis of Hi-C, ATAC-seq, CUT&RUN, and RNA-seq in primary human fibroblasts undergoing TIS induced by ionizing radiation (RAD) or bleomycin (BLEO). We show that TIS leads to global chromatin decompaction, weakened compartmentalization, and destabilization of topologically associated domains (TADs), alongside widespread loss and rewiring of chromatin loops. Notably, RAD and BLEO elicit distinct changes in distance-dependent compartment strength and enhancer-promoter (E-P) loop patterns, reflecting divergent 3D regulatory programs. Importantly, TIS reshapes the chromatin environment around senescence-associated secretory phenotype (SASP) genes, while their adjacent regions exhibit reduced chromatin interactions, allowing transcriptional activation. Our study reveals that 3D genome remodeling in TIS is highly plastic and context-dependent and discloses spatial regulation of gene expression during therapy-induced cellular senescence.
WOS关键词GENOME ; ORGANIZATION ; LANDSCAPE ; DAMAGE
资助项目Chinese Academy of Sciences[82130045] ; Chinese Academy of Sciences[82350710221] ; Chinese Academy of Sciences[82571777] ; National Natural Science Foundation of China ; National Key Research and Development Program of China
WOS研究方向Cell Biology ; Geriatrics & Gerontology
语种英语
WOS记录号WOS:001658604800015
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/322569]  
专题中国科学院上海药物研究所
通讯作者Zhang, Ge; Wei, Gang; Sun, Yu
作者单位1.Cedars Sinai Med Ctr, Ctr Adv Gerotherapeut, Pacific Design Ctr, West Hollywood, CA USA
2.Shanghai Jiao Tong Univ, Ctr Single Cell Om, Sch Publ Hlth, Sch Med, Shanghai, Peoples R China
3.Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA USA
4.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China
5.Binzhou Med Univ, Inst Aging Med, Sch Pharm, Yantai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Immun & Infect, Shanghai Inst Mat Med, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Ge,Zhang, Wei,Wang, Changxu,et al. Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy-Induced Senescent Cells[J]. AGING CELL,2026,25(1):21.
APA Zhang, Ge.,Zhang, Wei.,Wang, Changxu.,Jiang, Zhirui.,Xu, Qixia.,...&Sun, Yu.(2026).Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy-Induced Senescent Cells.AGING CELL,25(1),21.
MLA Zhang, Ge,et al."Spatial Reorganization of Chromatin Architecture Shapes the Expression Phenotype of Therapy-Induced Senescent Cells".AGING CELL 25.1(2026):21.

入库方式： OAI收割

来源：上海药物研究所

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