Apoptotic dysregulation mediates stem cell competition and tissue regeneration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 Nov 2023
20 Nov 2023
Historique:
received:
25
08
2022
accepted:
14
09
2023
medline:
22
11
2023
pubmed:
21
11
2023
entrez:
21
11
2023
Statut:
epublish
Résumé
Since adult stem cells are responsible for replenishing tissues throughout life, it is vital to understand how failure to undergo apoptosis can dictate stem cell behavior both intrinsically and non-autonomously. Here, we report that depletion of pro-apoptotic Bax protein bestows hair follicle stem cells with the capacity to eliminate viable neighboring cells by sequestration of TNFα in their membrane. This in turn induces apoptosis in "loser" cells in a contact-dependent manner. Examining the underlying mechanism, we find that Bax loss-of-function competitive phenotype is mediated by the intrinsic activation of NFκB. Notably, winner stem cells differentially respond to TNFα, owing to their elevated expression of TNFR2. Finally, we report that in vivo depletion of Bax results in an increased stem cell pool, accelerating wound-repair and de novo hair follicle regeneration. Collectively, we establish a mechanism of mammalian cell competition, which can have broad therapeutic implications for tissue regeneration and tumorigenesis.
Identifiants
pubmed: 37985759
doi: 10.1038/s41467-023-41684-x
pii: 10.1038/s41467-023-41684-x
pmc: PMC10662150
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
bcl-2-Associated X Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7547Subventions
Organisme : European Molecular Biology Organization (EMBO)
ID : YIP
Organisme : Israel Science Foundation (ISF)
ID : 2124/19
Informations de copyright
© 2023. The Author(s).
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