Year: 2023
Type: article
Abstract: 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.
Source: Developmental Cell
Authors: Qinghao Yu, Hannah E. Walters, Giovanni Pasquini, Sumeet Pal Singh, Martina Lachnit, Catarina R. Oliveira, Daniel León-Periñán, Andreas Petzold, Preethi Kesavan, Cristina Subiran Adrados, Ines Garteizgogeascoa, Dunja Knapp, Anne Wagner, Andrea Bernardos, María Alfonso, Gayathri Nadar, Alwin M. Graf, Konstantin E. Troyanovskiy, Andreas Dahl, Volker Busskamp, Ramón Martínez-Máñez, Maximina H. Yun
Institutions: Center for Regenerative Therapies Dresden, Technische Universität Dresden, University of Bonn, Université Libre de Bruxelles, Center for Information Services and High Performance Computing, DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Instituto de Salud Carlos III, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Investigación Biomédica en Red, Centro de Investigacion Principe Felipe, Universitat Politècnica de València, Max Planck Institute of Molecular Cell Biology and Genetics, Instituto de Investigación Sanitaria La Fe, Physics of Life
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,080
Funders: Alexander von Humboldt-Stiftung, Ministerio de Ciencia, Innovación y Universidades, European Commission, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Volkswagen Foundation, Fonds De La Recherche Scientifique - FNRS, Generalitat Valenciana, Zentrum für Regenerative Therapien Dresden, European Regional Development Fund, Agencia Estatal de Investigación
Awards: G1009292636, G231515103, Zelluläre und molekulare Grundlagen der de novo Regeneration des Thymus, G2772067330, G2811253794, G3103603086, G3453039274, G3620252990, G3802812302, G4403050208, G5356680776, G57265498, Wechselspiel zwischen Regeneration und Alterung beim Axolotl, einer Art mit vernachlässigbarer Seneszenz, G7364962080, G7869458481, FZT 111: Zentrum für Regenerative Therapien Dresden (CRTD), G8181105605, G8367532992, G8468379719, G87162555, EXC 2151: ImmunoSensation2 the immune sensory system, G922661841
OpenAlex ID: W4387911028