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

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

Blog Article

Abstract Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal Terminal Release Set 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 Detergents 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.