Unraveling the role of Djstat5 in regulating planarian regeneration through modulating cell proliferation and apoptosis

Signal transducer and activator of transcription (STAT) proteins are critical for converting extracellular stimuli into transcriptional programs that govern cellular homeostasis. Although extensively studied in mammals, the functions of STAT genes in invertebrates remain poorly understood. In this study, we investigated the role of Djstat5, a STAT5 homolog in the planarian Dugesia japonica, revealing its dynamic activation during wound response and regeneration initiation. The RNA interference (RNAi) knockdown of Djstat5 severely disrupted tissue regeneration, manifesting as blastemal hypoplasia coupled with attenuated mitotic and apoptotic dynamics. The transcriptomic analysis revealed that Djstat5 knockdown led to decreased expression of Djcbp (a chromatin regulator) and increased expression of Djnlrc3 (an inflammatory modulator). Furthermore, the results of double RNAi experiments demonstrated a functional antagonism between these downstream effectors, with Djcbp knockdown exacerbating while Djnlrc3 silencing ameliorating Djstat5-deficient phenotypes. In conclusion, our study highlights the critical role of Djstat5 in planarian regeneration and provides new insights into the underlying molecular mechanisms.