Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration

Cell fate stability is essential to maintaining law and orderin complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non -regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring so-matic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevents reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context results in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that pro-motes cellular reprogramming could provide an avenue to enhance regeneration.

Automated summary

Cell fate stability is important for complex animals but reduces plasticity and regenerative ability. Signals from senescent cells can reprogram neighboring cells into stem cells that drive whole-body regeneration. Understanding the effects of senescence on cellular reprogramming can enhance regeneration.