Discovery of Muscle-Tendon Progenitor Subpopulation in Human Myotendinous Junction at Single-Cell Resolution.
Discovery of Muscle-Tendon Progenitor Subpopulation in Human Myotendinous Junction at Single-Cell Resolution.
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DOI：
10.34133/2022/9760390
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Yan R;Zhang H;Ma Y;Lin R;Zhou B;Zhang T;Fan C;Zhang Y;Wang Z;Fang T;Yin Z;Cai Y;Ouyang H;Chen X
肌腱连接处是连接肌肉和肌腱的复杂而特殊的解剖区域，也是肌腱修复的关键。尽管如此，MTJ的解剖结构和连接结构，细胞的聚集和分布，以及哪些细胞参与修复组织仍然不清楚。在此，我们从单细胞水平分析了人类MTJ的细胞亚型分布和功能。我们确定了四种主要亚型，包括干细胞、肌肉、肌腱和肌肉-肌腱祖细胞（MTP）。MTP亚群保留了干细胞的特征，同时表达肌肉和肌腱标记基因，可能具有双向分化的潜力。我们还发现肌腱前体细胞呈透明杯状分布，肌细胞先连接到MTP，然后连接到肌腱。移植到MTJ损伤模型后，MTP表现出较强的再生能力。最后，我们还通过体外加入雷帕霉素和使用mTOR-ko小鼠的体内验证证明了mTOR信号传导对于MTP维持的重要性。我们的研究对肌腱连接处的异质性进行了全面分析，发现了一个特殊的称为MTP的簇，为肌腱连接处的生物学意义提供了新的见解，并为今后肌腱连接处再生修复的研究奠定了基础。
The myotendinous junction (MTJ) is a complex and special anatomical area that connects muscles and tendons, and it is also the key to repairing tendons. Nevertheless, the anatomical structure and connection structure of MTJ, the cluster and distribution of cells, and which cells are involved in repairing the tissue are still unclear. Here, we analyzed the cell subtype distribution and function of human MTJ at single-cell level. We identified four main subtypes, including stem cell, muscle, tendon, and muscle-tendon progenitor cells (MTP). The MTP subpopulation, which remains the characteristics of stem cells and also expresses muscle and tendon marker genes simultaneously, may have the potential for bidirectional differentiation. We also found the muscle-tendon progenitor cells were distributed in the shape of a transparent goblet; muscle cells first connect to the MTP and then to the tendon. And after being transplanted in the MTJ injury model, MTP exhibited strong regenerative capability. Finally, we also demonstrated the importance of mTOR signaling for MTP maintenance by in vitro addition of rapamycin and in vivo validation using mTOR-ko mice. Our research conducted a comprehensive analysis of the heterogeneity of myotendinous junction, discovered a special cluster called MTP, provided new insights into the biological significance of myotendinous junction, and laid the foundation for future research on myotendinous junction regeneration and restoration.
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影响因子：
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