轴突
胚芽
生物
衰老
Wnt信号通路
再生(生物学)
细胞生物学
祖细胞
祖细胞
干细胞
信号转导
作者
Qinghao Yu,Hannah Walters,Giovanni Pasquini,Sumeet Pal Singh,Martina Lachnit,Catarina R. Oliveira,Daniel León-Periñán,A. Petzold,Preethi Kesavan,Cristina Subiran Adrados,Inés Garteizgogeascoa Suñer,Dunja Knapp,Anne Wagner,Andrea Bernardos,María Alfonso,Gayathri Nadar,Alwin M. Graf,Konstantin E. Troyanovskiy,Andreas Dahl,Volker Busskamp,Ramón Martı́nez-Máñez,Maximina H. Yun
标识
DOI:10.1016/j.devcel.2023.09.009
摘要
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.
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