Research Article

Identification of a regeneration-organizing cell in the Xenopus tail

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Science  17 May 2019:
Vol. 364, Issue 6441, pp. 653-658
DOI: 10.1126/science.aav9996

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A tale of tadpole tail regeneration

Some vertebrates, including some amphibians, show a remarkable, if sometimes restricted, ability to regenerate lost appendages. Aztekin et al. compared naturally occurring regeneration-competent and -incompetent Xenopus laevis tadpoles using single-cell messenger RNA sequencing. They identified regeneration-organizing cells (ROCs) that could coordinate tail regeneration. Relocation of ROCs from the body to the amputation plane enabled specialized wound epidermis formation and subsequent regeneration. ROCs simultaneously expressed many different ligands that can induce proliferation of different progenitor cell populations. Thus, by signaling to underlying progenitors, ROCs orchestrate the growth of a new appendage.

Science, this issue p. 653


Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, which we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development and specifically relocalize to the amputation plane of regeneration-competent tadpoles, forming the wound epidermis. Genetic ablation or manual removal of ROCs blocks regeneration, whereas transplantation of ROC-containing grafts induces ectopic outgrowths in early embryos. Transcriptional profiling revealed that ROCs secrete ligands associated with key regenerative pathways, signaling to progenitors to reconstitute lost tissue. These findings reveal the cellular mechanism through which ROCs form the wound epidermis and ensure successful regeneration.

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