Induction and Characterization of Cellular Senescence in Salamanders

Yu, Qinghao; Walters, Hannah; Yun, Maximina H.

doi:10.1007/978-1-0716-2659-7_8

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…To study functional relationships between regeneration and senescence, we first employed an in vitro model of DNA damage-induced senescence in the axolotl limb mesenchyme-derived AL1 cell line 26 . Etoposide-treatment followed by sustained p53-stabilisation recapitulated a range of classical senescence phenotypes 4,27 , including expansion of lysosomal and mitochondrial networks, the induction of DNA damage markers, long-term proliferative arrest, and senescence-associated beta-galactosidase activity (SAβG) (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Control proliferating cells were seeded in parallel, treated with identical volumes of DMSO only, and passaged during the 12-day senescence induction to avoid confluence. Senescence induction was confirmed by positive SAβG staining, reduction in EdU incorporation, expansion of mitochondrial and lysosomal networks, and persistent DNA damage foci (MitoTracker, Lysomitotracker, γH2AX; 27 ).…”

Section: Methods Detailsmentioning

confidence: 95%

“…In vitro senescence induction was performed according to 27 , whereby cells were seeded at 50% confluence and subsequently exposed to 10 μM etoposide and 1 μM nutlin-3a for 24h. Cells were then incubated with 1 μM nutlin-3a in fresh media for the following 11 days.…”

Section: Methods Detailsmentioning

confidence: 99%

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Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Walters

Pasquini

et al. 2022

Preprint

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Axolotl limb regeneration is accompanied by the transient induction of cellular senescence within the blastema, the structure which nucleates regeneration. The precise role of this blastemal senescent cell (bSC) population, however, remains unknown. Here, through a combination of gain- and loss-of-function assays, we elucidate the functions and molecular features of cellular senescence in vivo. We demonstrate that cellular senescence plays a positive role during axolotl regeneration, by creating a pro-proliferative niche that supports progenitor cell expansion and blastema outgrowth. Mechanistically, these effects are mediated by the provision of Wnt ligands by bSCs. Further, we uncover a link between Wnt signalling and senescence induction, and propose that bSC-derived Wnt signals facilitate the proliferation of neighbouring cells in part by preventing their induction into senescence. This work defines the roles of cellular senescence in regeneration of complex structures.

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Section: Resultsmentioning

confidence: 99%

Section: Methods Detailsmentioning

confidence: 95%

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Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Walters

Pasquini

et al. 2022

Preprint

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“…In vitro senescence induction was performed according to Yu et al ( 2023 ), using UV‐irradiation (3 J/m 2 , UV Stratalinker) or 24‐h exposure to 20 μM etoposide, both followed by treatment with 1 μM Nutlin‐3a. Senescence induction following 12 days' treatment was confirmed by positive SA‐β‐gal staining, a significant reduction in EdU incorporation, expansion of mitochondrial and lysosomal networks and persistent DNA damage foci (Yu et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation

et al. 2023

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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.

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Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Yu,

Walters,

Pasquini

et al. 2023

Developmental Cell

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Induction and Characterization of Cellular Senescence in Salamanders

Cited by 3 publications

References 28 publications

Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation

Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

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