Cell senescence contributes to tissue regeneration in zebrafish.

Sabela Da Silva‐Álvarez,Laura Sánchez,Antón Barreiro‐Iglesias,Daniel Sobrido‐Cameán,Ana Quelle,Manuel Collado,Jorge Guerra‐Varela

doi:10.1111/acel.13052

Abstract

Cellular senescence is a stress response that limits the proliferation of damaged cells by establishing a permanent cell cycle arrest. Different stimuli can trigger senescence but excessive production or impaired clearance of these cells can lead to their accumulation during aging with deleterious effects. Despite this potential negative side of cell senescence, its physiological role as a pro‐regenerative and morphogenetic force has emerged recently after the identification of programmed cell senescence during embryogenesis and during wound healing and limb regeneration. Here, we explored the conservation of tissue injury‐induced senescence in a model of complex regeneration, the zebrafish. Fin amputation in adult fish led to the appearance of senescent cells at the site of damage, and their removal impaired tissue regeneration. Despite many conceptual similarities, this tissue repair response is different from developmental senescence. Our results lend support to the notion that cell senescence is a positive response promoting tissue repair and homeostasis.

Highlights

To study senescence after tissue damage, we amputated the pectoral fin of adult fish at ap‐ proximately 50% of its length and followed regeneration with time (Figure 1a)
We observed that 8 dpa was the time point that produced a stronger SAbetaGal reaction and this activity was restricted to the distal part of the fin, the area where regeneration takes place (Figure 1d)
We extracted RNA from amputated distal and proximal fins and unamputated fins, to check for the expression of some genes that have been linked to the induction of senescence in different species (Collado & Serrano, 2006; Hernandez‐Segura, Nehme, & Demaria, 2018) and in zebrafish (Donnini et al, 2010; Xia et al, 2014)

Summary

Introduction

To study senescence after tissue damage, we amputated the pectoral fin of adult fish (around 1 year old) at ap‐ proximately 50% of its length and followed regeneration with time (Figure 1a). We observed that 8 dpa was the time point that produced a stronger SAbetaGal reaction and this activity was restricted to the distal part of the fin, the area where regeneration takes place (Figure 1d).

Results

Conclusion