Reversine increases the plasticity of lineage-committed mammalian cells
Reversine increases the plasticity of lineage-committed mammalian cells
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DOI：
10.1073/pnas.0704360104
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发表时间：
2007-06-19
影响因子：
11.1
通讯作者：
Schultz, Peter G.
中科院分区：
文献类型：
--
作者：
Chen, Shuibing;Takanashi, Shinichi;Schultz, Peter G.
以前，一个小分子，reversine，被确定为逆转谱系承诺的小鼠成肌细胞到一个更原始的多能状态。在这里，我们表明，逆转录酶可以增加可塑性的C2C12成肌细胞在单细胞水平和逆转录酶处理的细胞获得的能力，分化成骨细胞和脂肪细胞的谱系特异性诱导条件下。此外，逆转录酶在多种细胞类型中具有活性，包括3T3E1成骨细胞和人原代骨骼肌成肌细胞。生物化学和细胞实验表明，reversine作为非肌肉肌球蛋白11重链和MEK 1的双重抑制剂发挥作用，并且这两种活性都是reversine作用所必需的。MEK 1和非肌肉肌球蛋白11重链的抑制导致细胞周期改变和组蛋白乙酰化状态的变化，但其他因素也可能有助于逆转录酶的活性，包括PI3K信号通路的激活。
Previously, a small molecule, reversine, was identified that reverses lineage-committed murine myoblasts to a more primitive multipotent state. Here, we show that reversine can increase the plasticity of C2C12 myoblasts at the single-cell level and that reversine-treated cells gain the ability to differentiate into osteoblasts and adipocytes under lineage-specific inducing conditions. Moreover, reversine is active in multiple cell types, including 3T3E1 osteoblasts and human primary skeletal myoblasts. Biochemical and cellular experiments suggest that reversine functions as a dual inhibitor of nonmuscle myosin 11 heavy chain and MEK1, and that both activities are required for reversine's effect. Inhibition of MEK1 and nonmuscle myosin 11 heavy chain results in altered cell cycle and changes in histone acetylation status, but other factors also may contribute to the activity of reversine, including activation of the PI3K signaling pathway.