Abstract
Stem cell differentiation is accompanied by an increase in mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine, and spermine that are essential for cell growth and stem cell maintenance. However, the role of polyamines as endogenous effectors of stem cell fate and whether they act through translational control remains obscure. Here, we investigated the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. HFSCs showed lower translation rates than progenitor cells, and a forced suppression of translation by direct targeting of the ribosome or through specific depletion of natural polyamines elevated stemness. In addition, we identified N1-acetylspermidine as a novel parallel regulator of cell fate decisions, increasing proliferation without reducing translation. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions.
Key Points
Low mRNA translation rates characterize hair follicle stem cell (HFSC) state
Depletion of natural polyamines enriches HFSCs via reduced translation
N1-acetylspermidine promotes HFSC state without reducing translation
N1-acetylspermidine expands the stem cell pool through elevated proliferation
Competing Interest Statement
The authors have declared no competing interest.