| First Author | Yusupova M | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 7547 |
| PubMed ID | 37985759 | Mgi Jnum | J:343605 |
| Mgi Id | MGI:7560894 | Doi | 10.1038/s41467-023-41684-x |
| Citation | Yusupova M, et al. (2023) Apoptotic dysregulation mediates stem cell competition and tissue regeneration. Nat Commun 14(1):7547 |
| abstractText | 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 TNFalpha 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 NFkappaB. Notably, winner stem cells differentially respond to TNFalpha, 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. |
