Single-cell RNA-seq reveals novel mitochondria-related musculoskeletal cell populations during adult axolotl limb regeneration process
Single-cell RNA-seq reveals novel mitochondria-related musculoskeletal cell populations during adult axolotl limb regeneration process
复制标题
单细胞RNA-seq揭示了成年蝾螈肢体再生过程中新的线粒体相关肌肉骨骼细胞群
DOI：
10.1038/s41418-020-00640-8
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发表时间：
2021
影响因子：
12.4
通讯作者：
Xiao Chen
中科院分区：
文献类型：
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作者：
Tian Qin;Chunmei Fan;Ting-zhang Wang;Heng Sun;Yanyan Zhao;Ruojin Yan;Long Yang;Weiliang Shen;Junxin Lin;Varitsara Bunpetch;Magali Cucchiarini;Nicholas D. Clement;Christopher E. Mason;Norimasa Nakamura;Rameah Bhonde;Zi Yin;Xiao Chen
虽然包括人类在内的哺乳动物再生组织或肢体的能力有限，但Axolotl能够在受伤后再生整个肢体和主要器官。创面成纤维细胞在肢体再生中已得到了广泛的研究。然而，由于细胞外基质和参与再生过程的细胞亚群的特征不充分，人类肢体再生的关键驱动因素的发现仍然未知。在这项研究中，我们应用大规模的单细胞RNA测序对成年Axolotl肢体再生过程中的细胞进行了分类，发现了一个新的再生特异性线粒体相关簇，通过提供能量来支持再生，以及通过细胞间相互作用信号促进细胞外基质分泌(CoL2+)簇促进再生。我们还发现了COL1+/COL2+细胞亚群的去分化和再分化，并揭示了支持肌肉骨骼系统再生的COL2-线粒体亚群。在这些发现的基础上，我们重建了成年轴突肢体再生过程的动态单细胞转录组，并鉴定了新的再生线粒体相关肌肉骨骼种群，从而对再生微环境中细胞簇之间的关键相互作用有了更深入的了解。
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.