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

Author

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  • Zhifei Zhang

    (Tongji University)

  • Haiyan Yang

    (Tongji University)

  • Lei Fang

    (Tongji University)

  • Guangrong Zhao

    (Tongji University)

  • Jun Xiang

    (Tongji University School of Medicine)

  • Jialin C. Zheng

    (Tongji Hospital Affiliated to Tongji University
    Tongji University
    Tongji University
    Shanghai Fourth People’s Hospital affiliated to Tongji University School of Medicine)

  • Zhao Qin

    (Tongji University
    Tongji University
    Tongji University)

Abstract

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.

Suggested Citation

  • Zhifei Zhang & Haiyan Yang & Lei Fang & Guangrong Zhao & Jun Xiang & Jialin C. Zheng & Zhao Qin, 2024. "DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49318-6
    DOI: 10.1038/s41467-024-49318-6
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    References listed on IDEAS

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    1. Cynthia J. Kenyon, 2010. "The genetics of ageing," Nature, Nature, vol. 464(7288), pages 504-512, March.
    2. Cynthia J. Kenyon, 2010. "Erratum: The genetics of ageing," Nature, Nature, vol. 467(7315), pages 622-622, September.
    3. Zhao Qin & E. Jane Albert Hubbard, 2015. "Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    4. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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