Induction of growth arrest and polycomb gene expression by reversine allows C2C12 cells to be reprogrammed to various differentiated cell types
Induction of growth arrest and polycomb gene expression by reversine allows C2C12 cells to be reprogrammed to various differentiated cell types
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DOI：
10.1002/pmic.200700636
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发表时间：
2007-12-01
期刊：
影响因子：
3.4
通讯作者：
Lee, Kenneth K. H.
中科院分区：
文献类型：
--
作者：
Shan, Sze Wan;Tang, Mei Kuen;Lee, Kenneth K. H.
Reversine是一种小的、细胞可渗透的合成化学物质，具有将C2C12肌原细胞重编程为各种分化细胞类型的能力。然而，我们仍然不知道逆转录酶是如何工作的，也不知道所涉及的基因和蛋白质。因此，我们使用比较蛋白质组学技术来解决这个问题。我们已经确定了几个蛋白质，与细胞周期的进展，下调逆转录。同时，有蛋白质与生长停滞的诱导上调。因此，我们研究了逆转录酶对C2C12细胞生长的影响，并确定其抑制细胞生长。逆转对细胞存活的影响很小。我们还研究了多梳基因、多梳抑制复合物1（PHC1）和Ezh2的表达是否受到逆转录酶的影响。多梳组基因通常参与基于染色质的基因沉默。我们发现，PHC1和Ezh2的表达增强逆转，它与肌肉特异性转录因子基因，肌细胞生成素，MyoD，和Myf5的抑制。因此，我们认为逆转录酶能够通过诱导细胞生长停滞和促进PHC1和Ezh2表达将C2C12细胞重编程为各种分化的细胞类型。
Reversine is a small, cell permeable synthetic chemical that has the ability to reprogram C2C12 myogenic cells to become various differentiated cell types. However, we still do not know how reversine works or the genes and proteins involved. Hence, we have used comparative proteomic techniques to address this issue. We have identified several proteins that were associated with cell cycle progression which were downregulated by reversine. Simultaneously, there were proteins associated with the induction of growth arrest that were upregulated. Consequently, we investigated the effects of reversine on C2C12 cell growth and established that it inhibited cell growth. Reversine had little affects on cell survival. We also investigated whether expressions of the polycomb genes, polycomb repressive complex 1 (PHC1) and Ezh2, were affected by reversine. Polycomb group genes are normally involved in chromatin based gene silencing. We found that PHC1 and Ezh2 expressions were enhanced by reversine and that it correlated with the inhibition of muscle specific transcriptional factor genes, myogenin, MyoD, and Myf5. Therefore, we believe that reversine is able to reprogram C2C12 cells to various differentiated cell types by inducing cell growth arrest, and promoting PHC1 and Ezh2 expressions.