Apoptotic dysregulation mediates stem cell competition and tissue regeneration
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 follic...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41684-x |
| _version_ | 1797452127331680256 |
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| author | Marianna Yusupova Roi Ankawa Yahav Yosefzon David Meiri Ido Bachelet Yaron Fuchs |
| author_facet | Marianna Yusupova Roi Ankawa Yahav Yosefzon David Meiri Ido Bachelet Yaron Fuchs |
| author_sort | Marianna Yusupova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:04:17Z |
| format | Article |
| id | doaj.art-c051d054abb647e790758fb8ec3934dd |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T15:04:17Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c051d054abb647e790758fb8ec3934dd2023-11-26T13:44:27ZengNature PortfolioNature Communications2041-17232023-11-0114112010.1038/s41467-023-41684-xApoptotic dysregulation mediates stem cell competition and tissue regenerationMarianna Yusupova0Roi Ankawa1Yahav Yosefzon2David Meiri3Ido Bachelet4Yaron Fuchs5Faculty of Biology, Technion-Israel Institute of TechnologyFaculty of Biology, Technion-Israel Institute of TechnologyFaculty of Biology, Technion-Israel Institute of TechnologyFaculty of Biology, Technion-Israel Institute of TechnologyAugmanityFaculty of Biology, Technion-Israel Institute of TechnologyAbstract 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.https://doi.org/10.1038/s41467-023-41684-x |
| spellingShingle | Marianna Yusupova Roi Ankawa Yahav Yosefzon David Meiri Ido Bachelet Yaron Fuchs Apoptotic dysregulation mediates stem cell competition and tissue regeneration Nature Communications |
| title | Apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| title_full | Apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| title_fullStr | Apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| title_full_unstemmed | Apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| title_short | Apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| title_sort | apoptotic dysregulation mediates stem cell competition and tissue regeneration |
| url | https://doi.org/10.1038/s41467-023-41684-x |
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