Ezh2 Is Essential for Patterning of Multiple Musculoskeletal Tissues but Dispensable for Tendon Differentiation.
Ezh2 Is Essential for Patterning of Multiple Musculoskeletal Tissues but Dispensable for Tendon Differentiation.
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Ezh2 对于多个肌肉骨骼组织的模式化至关重要，但对于肌腱分化来说是可有可无的。
DOI：
10.1089/scd.2020.0209
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发表时间：
2021
影响因子：
4
通讯作者：
Schweitzer,Ronen
中科院分区：
文献类型：
--
作者：
Pal,Deepanwita;Riester,ScottM;Hasan,Bashar;Tufa,SaraF;Dudakovic,Amel;Keene,DouglasR;vanWijnen,AndreJ;Schweitzer,Ronen
高效的肌肉骨骼系统取决于肌肉、骨骼和肌腱的精确组装以及协调的生长和功能。然而，驱动肌肉骨骼综合发育以及这些组织协调生长和分化的机制仍不清楚。表观遗传修饰剂已成为细胞命运分化的关键调节剂，但迄今为止，人们对它们在肌腱生物学中的作用几乎一无所知。先前的研究表明，由主要组蛋白甲基转移酶增强子 zeste 同源物 2 (EZH2) 驱动的表观遗传修饰在脊椎动物发育中具有重要作用，包括骨骼模式和骨形成。我们现在发现，通过肢体间充质靶向 Ezh2 对肌腱和肌肉模式也有显着影响，这可能反映了 Ezh2 介导的早期间充质线索对于肌肉骨骼系统所有组织的协调模式和发育的重要作用。相反，肌腱细胞中 Ezh2 的缺失不会破坏整体肌腱结构或胶原蛋白组织，表明肌腱分化和成熟独立于 Ezh2 信号传导。
An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton, and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targetingEzh2through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated byEzh2for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss ofEzh2in the tendon cells did not disrupt overall tendon structure or collagen organization suggesting that tendon differentiation and maturation are independent ofEzh2signaling.