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Mosteiro, L., Pantoja, C., & Alcazar, N. (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science, 354(6315), aaf4445. Added by: Dr. Enrique Feoli (02/07/2025, 21:55) Last edited by: Dr. Enrique Feoli (02/07/2025, 22:05) |
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| Resource type: Journal Article DOI: 10.1126/science.aaf4445 BibTeX citation key: Mosteiro2016 View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp Subcategories: Cell plasticity, Paligenosis Creators: Alcazar, Mosteiro, Pantoja Collection: Science |
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| Abstract |
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Differentiated cells in a culture dish can assume a new identity when manipulated to express four transcription factors. This “reprogramming” process has sparked interest because conceivably it could be harnessed as a therapeutic strategy for tissue regeneration. Mosteiro et al. used a mouse model to study the signals that promote cell reprogramming in vivo. They found that the factors that trigger reprogramming in vitro do the same in vivo; however, they also inflict cell damage. The damaged cells enter a state of senescence and begin secreting certain factors that promote reprogramming, including an inflammatory cytokine called interleukin-6. Thus, in the physiological setting, cell senescence may create a tissue context that favors reprogramming of neighboring cells. Science, this issue p. 10.1126/science.aaf4445 In mice, senescent cells created by tissue damage induce reprogramming of neighboring cells, enhancing tissue repair. Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity. Genetic and pharmacological analyses indicate that OSKM-induced senescence requires the Ink4a/Arf locus and, through the production of the cytokine interleukin-6, creates a permissive tissue environment for in vivo reprogramming. Biological conditions linked to senescence, such as tissue injury or aging, favor in vivo reprogramming by OSKM. These observations may be relevant for tissue repair.
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| Notes |
Expression of OSKM in vivo, apart from inducing the reprogramming of a small population of cells, also induces damage and senescence in many other cells. Senescent cells release factors that promote the reprogramming of neighboring cells, with IL-6 being a critical mediator. Tissue injury and aging, through the accumulation of senescent cells, favor in vivo reprogramming. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |