Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Research output: Contribution to journalResearch articleContributedpeer-review



Axolotl limb regeneration is accompanied by the transient induction of cellular senescence within the blastema, the structure that 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. Senescent cells impact their microenvironment via Wnt pathway modulation. Further, we identify a link between Wnt signaling and senescence induction and propose that bSC-derived Wnt signals facilitate the proliferation of neighboring cells in part by preventing their induction into senescence. This work defines the roles of cellular senescence in the regeneration of complex structures.


Original languageEnglish
Pages (from-to)2416-2427.e7
JournalDevelopmental cell
Issue number22
Publication statusPublished - 20 Nov 2023

External IDs

Scopus 85177051739
ORCID /0000-0001-9599-8632/work/150329182



  • Animals, Ambystoma mexicanum/metabolism, Cellular Senescence, Wnt Signaling Pathway, Stem Cells, Cell Proliferation, Extremities