Apoptotic dysregulation mediates stem cell competition and tissue regeneration

Marianna Yusupova, Roi Ankawa, Yahav Yosefzon, David Meiri, Ido Bachelet, Yaron Fuchs

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number7547
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - 20 Nov 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

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