Identification of a regeneration-organizing cell in the Xenopus tail

Identification of a regeneration-organizing cell in the Xenopus tail
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DOI:
10.1126/science.aav9996
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发表时间:
2019-05-17
期刊:
影响因子:
56.9
通讯作者:
Jullien, J.
Jullien, J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Aztekin, C.;Hiscock, T. W.;Jullien, J.

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与哺乳动物不同,非洲爪哇蝌蚪具有很高的再生潜力。为了表征这种再生反应,我们在尾巴截断后进行了单细胞RNA测序。通过比较自然产生的具有再生能力和不具备再生能力的蝌蚪,我们确定了一种以前未被识别的细胞类型,我们称之为再生组织细胞(ROC)。在正常的尾巴发育过程中,ROC存在于表皮中,并特异性地重新定位到具有再生能力的蝌蚪的截肢平面上,形成伤口表皮。基因消融或手动切除ROC会阻止再生,而含有ROC的移植物移植会诱导早期胚胎异位生长。转录图谱显示,ROCs分泌与关键再生途径相关的配体,向祖细胞发出信号以重建丢失的组织。这些发现揭示了ROCs形成创面表皮并确保成功再生的细胞机制。
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.