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Peer-reviewedCC BY 4.0PLOS Biology

Regional signaling controls stem cell-mediated regeneration in an invertebrate chordate

  • Tal Gordon1
  • Tom Levy2
  • Chester Jiamu Yu3
  • Benyamin Rosental4
  • Lauren Lubeck5
  • Lucia Manni
  • Irving L. Weissman
  • Ayelet Voskoboynik
5 affiliations
  1. 1Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, California, United States of America
  2. 2Hopkins Marine Station, Stanford University, Pacific Grove, California, United States of America
  3. 3Biology Department, Padova University, Padova, Italy
  4. 4Department of Biology, Stanford University, Stanford, California, United States of America
  5. 5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Center for Regenerative Medicine and Stem Cells, Ben Gurion University of the Negev, Beer-Sheva, Israel
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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 is associated with divergent regenerative outcomes, highlighting principles that may inform strategies to enhance tissue repair in other systems.

Many tissues harbor quiescent stem cells that are activated upon injury, yet how local signals regulate this transition remains unclear. This study shows that there are significant differences in the injury response by a stem cell population depending on region-specific signalling cues in the tunicate Ciona robusta.

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Cite

BibTeXRIS
BibTeX
@article{gordon2026regional,
  title = {{Regional signaling controls stem cell-mediated regeneration in an invertebrate chordate}},
  author = {Tal Gordon and Tom Levy and Chester Jiamu Yu and Benyamin Rosental and Lauren Lubeck and Lucia Manni and Irving L. Weissman and Ayelet Voskoboynik},
  journal = {PLOS Biology},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pbio.3004000},
  url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004000},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Regional signaling controls stem cell-mediated regeneration in an invertebrate chordate
AU  - Tal Gordon
AU  - Tom Levy
AU  - Chester Jiamu Yu
AU  - Benyamin Rosental
AU  - Lauren Lubeck
AU  - Lucia Manni
AU  - Irving L. Weissman
AU  - Ayelet Voskoboynik
PY  - 2026
DA  - 2026/09/18
JO  - PLOS Biology
DO  - 10.1371/journal.pbio.3004000
UR  - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004000
AB  - 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 is associated with divergent regenerative outcomes, highlighting principles that may inform strategies to enhance tissue repair in other systems.  Many tissues harbor quiescent stem cells that are activated upon injury, yet how local signals regulate this transition remains unclear. This study shows that there are significant differences in the injury response by a stem cell population depending on region-specific signalling cues in the tunicate Ciona robusta.
SN  - 1545-7885
ER  -