DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells

被引：0
作者：
Zhang, Zhifei [1 ]
Yang, Haiyan [1 ]
Fang, Lei [1 ]
Zhao, Guangrong [1 ]
Xiang, Jun [2 ]
Zheng, Jialin C. [3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ]
Qin, Zhao [1 ,8 ,9 ]
机构：
[1] Tongji Univ, Tongji Hosp, Sch Med, Orthoped Dept,Key Lab Spine & Spinal Cord Injury R, Shanghai 200065, Peoples R China
[2] Tongji Univ, Tongji Hosp, Sch Med, Dept Urol, Shanghai 200065, Peoples R China
[3] Tongji Univ, Tongji Hosp, Ctr Translat Neurodegenerat & Regenerat Therapy, Shanghai 200065, Peoples R China
[4] Tongji Univ, Shanghai East Hosp, Sch Med, State Key Lab Cardiol, Shanghai 200120, Peoples R China
[5] Tongji Univ, Med Innovat Ctr, Shanghai 200120, Peoples R China
[6] Tongji Univ, Shanghai Peoples Hosp 4, Sch Med, Shanghai Key Lab Anesthesiol & Brain Funct Modulat, Shanghai 200080, Peoples R China
[7] Tongji Univ, Shanghai Peoples Hosp 4, Translat Res Inst Brain & Brain Like Intelligence, Sch Med, Shanghai 200080, Peoples R China
[8] Tongji Univ, Innovat Ctr Med Basic Res Brain Aging & Associated, Minist Educ, Shanghai 200331, Peoples R China
[9] Tongji Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200331, Peoples R China
[10] Tongji Univ, Shanghai Frontiers Sci Ctr Nanocatalyt Med, Sch Med, Shanghai 200331, Peoples R China
来源：
NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期
基金：
中国国家自然科学基金;
关键词：
STEM-CELLS; NOTCH; MECHANISMS; MEMBRANE; GENETICS; GROWTH; OOCYTE; GENES;
D O I：
10.1038/s41467-024-49318-6
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.
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页数：13
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