Large-Scale Clustered Transcriptional Silencing Associated With Cellular Senescence

被引:0
作者
Gurkar, Aditi U. [1 ,2 ,3 ]
Okawa, Satoshi [2 ,4 ,5 ,6 ]
Guillermier, Christelle [7 ]
Chaddha, Kritika [1 ,2 ]
Steinhauser, Matthew L. [1 ,2 ,8 ]
机构
[1] UPMC, Aging Inst, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA
[3] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15260 USA
[4] Univ Pittsburgh, Sch Med, Ctr Pulm Vasc Biol & Med, Pittsburgh Heart Lung Blood & Vasc Med Inst,Div Ca, Pittsburgh, PA 15260 USA
[5] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA
[6] Univ Pittsburgh, Sch Med, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA
[7] Brigham & Womens Hosp, Ctr Nanoimaging, Dept Med, Div Genet, Cambridge, MA USA
[8] Univ Pittsburgh, Dept Med, Div Cardiovasc Med, Sch Med, Pittsburgh, PA 15260 USA
基金
美国安德鲁·梅隆基金会;
关键词
aging; cellular senescence; imaging mass spectrometry; scRNA-seq; transcription;
D O I
10.1111/acel.70015
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Senescence is a cell fate associated with age-related pathologies; however, senescence markers are not well-defined. Using single cell multi-isotope imaging mass spectrometry (MIMS), we identified hypercondensed, transcriptionally silent DNA globules in a senescence model induced by dysfunctional telomeres. This architectural phenomenon was associated with geographically clustered transcriptional repression across somatic chromosomes with over-representation of cell cycle genes. Senescence-stimuli was associated with a higher frequency of cells that exhibited geographically concentrated transcriptional repression relative to control cells. This phenomenon was also observed in multiple other senescence models, including replicative senescence and irradiation. We further identified an enrichment of common pathways in all models of senescence, suggesting a common cellular response to this silencing phenomenon. Such large-scale clustered silencing of chromosomal segments rather than individual genes may explain senescence heterogeneity and a putative trajectory toward deep, irreversible senescence.
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页数:7
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