Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Salamanders are able to regenerate their entire limbs throughout lifespan, through a process that involves significant modulation of cellular plasticity. Limb regeneration is accompanied by the endogenous induction of cellular senescence, a state of irreversible cell cycle arrest associated with profound non-cell-autonomous consequences. While traditionally associated with detrimental physiological effects, here, we show that senescent cells can enhance newt limb regeneration. Through a lineage tracing approach, we demonstrate that exogenously derived senescent cells promote dedifferentiation of mature muscle tissue to generate regenerative progenitors. In a paradigm of newt myotube dedifferentiation, we uncover that senescent cells promote myotube cell cycle re-entry and reversal of muscle identity via secreted factors. Transcriptomic profiling and loss of function approaches identify the FGF-ERK signalling axis as a critical mediator of senescence-induced muscle dedifferentiation. While chronic senescence constrains muscle regeneration in physiological mammalian contexts, we thus highlight a beneficial role for cellular senescence as an important modulator of dedifferentiation, a key mechanism for regeneration of complex structures.
Details
Original language | English |
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Article number | e13826 |
Journal | Aging cell |
Volume | 22 |
Issue number | 6 |
Publication status | Published - 6 Apr 2023 |
Peer-reviewed | Yes |
External IDs
Scopus | 85152052177 |
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PubMed | 37025070 |
WOS | 000964872800001 |
Keywords
Research priority areas of TU Dresden
DFG Classification of Subject Areas according to Review Boards
ASJC Scopus subject areas
Keywords
- cellular senescence, dedifferentiation, ERK, FGF, regeneration, reprogramming, salamander, WNT, Cell Dedifferentiation, Mammals, Animals, Cellular Senescence, Salamandridae/physiology, Muscle Fibers, Skeletal/metabolism, Fgf, Cellular senescence, Regeneration, Reprogramming, Dedifferentiation, Salamander, Wnt, Erk