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.

中文翻译：

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N1-乙酰亚精胺是毛囊干细胞命运的决定因素。

干细胞分化伴随着 mRNA 翻译的增加。蛋白质生物合成速率受多胺腐胺、亚精胺和精胺的影响，它们对细胞生长和干细胞维持至关重要。然而，多胺作为干细胞命运的内源性效应物的作用以及它们是否通过翻译控制起作用仍然不清楚。在这里，我们使用毛囊干细胞 (HFSC) 类器官研究多胺在干细胞命运决定中的作用。与祖细胞相比，HFSCs 的翻译率较低，这与多胺水平降低有关。令人惊讶的是，整体多胺消耗减少了翻译，但不影响细胞命运。相反，由亚精胺/精胺 N1-乙酰转移酶 (SSAT; 也称为 SAT1) 激活并没有减少翻译但增强了词干性。这些结果表明多胺在细胞命运调节中的翻译独立作用。事实上，我们将 N1-乙酰亚精胺确定为细胞命运的决定因素，它通过增加自我更新起作用，并观察到在体内脱毛介导的 HFSC 增殖和分化时 N1-乙酰亚精胺水平升高。总体而言，这项研究描绘了多胺代谢介导的干细胞命运决定调节的多种途径。本文与该论文的第一作者进行了相关的第一人称采访。我们将 N1-乙酰亚精胺确定为通过增加自我更新起作用的细胞命运的决定因素，并观察到在体内脱毛介导的 HFSC 增殖和分化时 N1-乙酰亚精胺水平升高。总体而言，这项研究描绘了多胺代谢介导的干细胞命运决定调节的多种途径。本文与该论文的第一作者进行了相关的第一人称采访。我们将 N1-乙酰亚精胺确定为通过增加自我更新起作用的细胞命运的决定因素，并观察到在体内脱毛介导的 HFSC 增殖和分化时 N1-乙酰亚精胺水平升高。总的来说，这项研究描绘了多胺代谢介导的干细胞命运决定调节的多种途径。本文与该论文的第一作者进行了相关的第一人称采访。