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Identification of a regeneration-organizing cell in the Xenopus tail

Accepted version
Peer-reviewed

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Abstract

Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing (scRNA-seq) following tail amputation. By comparing naturally-occurring regeneration-competent and incompetent tadpoles, we identified a previously unrecognized cell type that 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.

Description

Keywords

Animals, Epidermal Cells, Epidermis, Re-Epithelialization, Sequence Analysis, RNA, Single-Cell Analysis, Tail, Transcriptome, Xenopus Proteins, Xenopus laevis

Journal Title

Science

Conference Name

Journal ISSN

0036-8075
1095-9203

Volume Title

Publisher

American Association for the Advancement of Science
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (105031/D/14/Z)
Royal Society (RP/R1/180165)
Wellcome Trust (101050/Z/13/Z)
Medical Research Council (MR/P000479/1)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Medical Research Council (MC_PC_12009)
Wellcome Trust (101050/Z/13/A)
Wellcome Trust Royal Society Cancer Research UK