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N1-acetylspermidine is a determinant of hair follicle stem cell fate.

ABSTRACT: Stem cell differentiation is accompanied by increased mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine and spermine, which 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 investigate the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. Compared to progenitor cells, HFSCs showed lower translation rates, correlating with reduced polyamine levels. Surprisingly, overall polyamine depletion decreased translation but did not affect cell fate. In contrast, specific depletion of natural polyamines mediated by spermidine/spermine N1-acetyltransferase (SSAT; also known as SAT1) activation did not reduce translation but enhanced stemness. These results suggest a translation-independent role of polyamines in cell fate regulation. Indeed, we identified N1-acetylspermidine as a determinant of cell fate that acted through increasing self-renewal, and observed elevated N1-acetylspermidine levels upon depilation-mediated HFSC proliferation and differentiation in vivo. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions. This article has an associated First Person interview with the first author of the paper.

SUBMITTER: Allmeroth K

PROVIDER: S-EPMC8182411 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Effect of N1-acetylspermidine treatment on hair follicle stem cell organoid cultures

Project description:Stem cell differentiation has been shown to involve an increase in mRNA translation. Amongst others, the rate of translation is influenced by availability of the natural polyamines putrescine, spermidine, and spermine that are essential for cell growth and modulate stem cell maintenance. However, the link between polyamines and translation in cell fate decisions remains obscure. Here, we used hair follicle stem cell (HFSC) organoids to study the role of polyamines as key regulators of mRNA translation in stem cell fate decisions. HFSCs showed lower translation 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. To identify the molecular mechanism by which N1-AcSpd supplementation promotes stemness, we performed RNA-sequencing. We unravel an increase in proliferation. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions.

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Effect of N1-acetylspermidine treatment on the translatome of hair follicle stem cell organoid cultures

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Effect of N1-acetylspermidine treatment on hair follicle stem cell organoid cultures

Project description:Effect of N1-acetylspermidine treatment on hair follicle stem cell organoid cultures

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IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation.

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Project description:Effect of N1-acetylspermidine treatment on the translatome of hair follicle stem cell organoid cultures

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Thyroid hormone signaling controls hair follicle stem cell function.

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Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle.

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Lactate dehydrogenase activity drives hair follicle stem cell activation.

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