N1-acetylspermidine is a determinant of hair follicle stem cell fate.
Cell fate
Hair follicle stem cells
Polyamines
mRNA translation
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
received:
05
08
2020
accepted:
20
03
2021
entrez:
11
5
2021
pubmed:
12
5
2021
medline:
13
7
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33973637
pii: 261953
doi: 10.1242/jcs.252767
pmc: PMC8182411
pii:
doi:
Substances chimiques
Spermine
2FZ7Y3VOQX
Acetyltransferases
EC 2.3.1.-
Spermidine
U87FK77H25
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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