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bioRxiv · 10.1101/2025.09.25.678506

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

Gordon, T.·Levy, T.·Yu, C. J.·Rosental, B.·Lubeck, L.·Manni, L.·Weissman, I. L.·Voskoboynik, A.
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Abstract

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 bottom body fragments regenerate while upper fragments fail to do so. By comparing these regenerative and non-regenerative contexts, 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.

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Gordon, T., Levy, T., Yu, C. J., Rosental, B., Lubeck, L., Manni, L., Weissman, I. L., Voskoboynik, A.. 2025-09-25. Regional Signaling Controls Stem Cell-Mediated Regeneration in an Invertebrate Chordate. https://doi.org/10.1101/2025.09.25.678506

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