Cellular senescence modulates progenitor cell expansion during axolotl limb regeneration

Autor: Qinghao Yu, Hannah E. Walters, Giovanni Pasquini, Sumeet Pal Singh, Daniel León-Periñán, Andreas Petzold, Preethi Kesavan, Cristina Subiran, Ines Garteizgogeascoa, Dunja Knapp, Anne Wagner, Andrea Bernardos, María Alfonso, Gayathri Nadar, Andreas Dahl, Volker Busskamp, Ramón Martínez-Máñez, Maximina H. Yun
Rok vydání: 2022
DOI: 10.1101/2022.09.01.506196
Popis: SUMMARYAxolotl 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.
Databáze: OpenAIRE