Abstract
While the capacity to regenerate tissues or limbs is limited in mammals, including humans, axolotls are able to regrow entire limbs and major organs after incurring a wound. The wound blastema has been extensively studied in limb regeneration. However, due to the inadequate characterization of ECM and cell subpopulations involved in the regeneration process, the discovery of the key drivers for human limb regeneration remains unknown. In this study, we applied large-scale single-cell RNA sequencing to classify cells throughout the adult axolotl limb regeneration process, uncovering a novel regeneration-specific mitochondria-related cluster supporting regeneration through energy providing and the ECM secretion (COL2+) cluster contributing to regeneration through cell–cell interactions signals. We also discovered the dedifferentiation and re-differentiation of the COL1+/COL2+ cellular subpopulation and exposed a COL2-mitochondria subcluster supporting the musculoskeletal system regeneration. On the basis of these findings, we reconstructed the dynamic single-cell transcriptome of adult axolotl limb regenerative process, and identified the novel regenerative mitochondria-related musculoskeletal populations, which yielded deeper insights into the crucial interactions between cell clusters within the regenerative microenvironment.
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Acknowledgements
This work was supported by the National key research and development program of China [2017YFA0104902]; and the National Natural Science Foundation of China (NSFC) grants [81972099, 81871764, 82072463, 81522029, 81772418, 31570987, 81330041, 81401781, 81572157]. Zhejiang Provincial Natural Science Foundation of China (LR20H060001). Fundamental Research Funds for the Central Universities. Written on behalf of the AME Translational Medicine Collaborative Group. We are grateful to the Core Facilities of Zhejiang University School of Medicine, and Bio-Ultrastructure Analysis Lab. of Analysis Center of Agrobiology and Environmental Sciences of the Zhejiang University for technical assistance.
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Qin, T., Fan, Cm., Wang, Tz. et al. Single-cell RNA-seq reveals novel mitochondria-related musculoskeletal cell populations during adult axolotl limb regeneration process. Cell Death Differ 28, 1110–1125 (2021). https://doi.org/10.1038/s41418-020-00640-8
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DOI: https://doi.org/10.1038/s41418-020-00640-8
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