Progress on the telomere-telomerase system in planarian neoblasts homeostasis and regeneration.

Planarians are flatworms with remarkable regenerative abilities, and their adult pluripotent stem cells, known as neoblasts, serve as the foundation for this regeneration. Neoblasts can rapidly migrate, proliferate, and undergo directed differentiation following tissue injury to complete regeneration. Telomeres are located at the ends of eukaryotic chromosomes and play a core role in maintaining chromosomal integrity. With each cell division, telomeres shorten. Telomerase is a reverse transcriptase that compensates for telomere loss during cell division by extending telomeric repeats. The telomere-telomerase system is one of the important mechanisms for maintaining stem cell homeostasis. As adult pluripotent stem cells of planarians, neoblasts are required to maintain a dynamic balance between high-frequency cell division and multilineage differentiation. The maintenance of their long-term proliferative capacity and genomic stability may depend on the precise regulation of the telomere-telomerase system. Thus, this system represents a critical entry point for understanding the remarkable regenerative ability of planarians. Integrating recent progress in regeneration, neoblast regulation, and the telomere-telomerase system, we systematically summarize the emerging evidence for telomere- telomerase involvement in neoblast homeostasis and regeneration. We aim to provide insights for research in regenerative medicine, stem cell regulation, and neural injury repair.