Regional Signaling Controls Stem Cell-Mediated Regeneration in an Invertebrate Chordate

Many tissues harbor quiescent stem cells that activate after injury, yet how local signals regulate this transition is not well understood. The solitary ascidian Ciona robusta provides a unique model, as upper body fragments regenerate while lower fragments fail to do so. By comparing these regenerative and non-regenerative fragments, we reveal striking differences in transcriptional dynamics and signaling environments. Combining flow cytometry, scRNA-seq, transplantation, and fate mapping, we identified a candidate stem cell population with robust proliferative and differentiation potential following transplantation. However, regenerative capacity does not simply reflect stem cell abundance, but instead depends on region-specific signaling cues. Local expression of metabolic, immune and differentiation-related factors further underscores the importance of spatially distinct environments in shaping outcomes. Our findings show how a shared injury response can diverge into regeneration versus failure, highlighting principles that may be leveraged to enhance tissue repair in other systems.