The stress-associated small heat shock protein affects stem cell proliferation, differentiation, and tissue-specific transcriptional networks during regeneration in Dugesia japonica

Abstract

Small heat shock proteins (sHSPs) represent a highly conserved family of molecular chaperones primarily known for their roles in protein homeostasis and stress responses. However, their involvement in regulating stem cell dynamics and tissue regeneration remains insufficiently characterized, particularly in planarians, a model organism renowned for its extraordinary regenerative capacity. In planarians, regeneration is driven by pluripotent stem cells, referred to as neoblasts, which are the only proliferative cells responsible for tissue repair and homeostasis. In this study, we identified a novel sHSP, DjsHSP, in Dugesia japonica and investigated its functional role in regeneration. Using RNA interference (RNAi), we demonstrated that DjsHSP knockdown significantly delayed regeneration of the blastema, intestine, eyes, and neural tissue. Mechanistically, DjsHSP knockdown disrupted neoblasts dynamics, leading to abnormal proliferation and impaired differentiation. This was associated with altered expression of lineage-specific transcription factors critical for triploblastic tissue differentiation. Furthermore, the knockdown of DjsHSP downregulated key transcription factors regulating organ-specific regeneration, contributing to defective tissue regeneration. These findings suggest that DjsHSP affects stem cell fate and organ regeneration by maintaining the balance between stem cell proliferation and differentiation and modulating tissue-specific transcriptional networks. Our study provides new insights into the molecular mechanisms underlying planarian regeneration, with potential implications for advancing regenerative medicine.