N1-acetylspermidine is a Determinant of Hair Follicle Stem Cell Fate

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2021 May 11

PMID 33973637

Citations 6

Authors

Kira Allmeroth

Christine S Kim

Andrea Annibal

Andromachi Pouikli

Janis Koester

Maxime J Derisbourg

Carlos Andres Chacon-Martinez

Christian Latza

Adam Antebi

Peter Tessarz

Sara A Wickstrom

Martin S Denzel

Affiliations

Soon will be listed here.

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.

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