The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells
The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells
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DOI：
10.1016/j.bbrc.2012.03.041
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发表时间：
2012-04-13
影响因子：
3.1
通讯作者：
Tooyama, Ikuo
中科院分区：
文献类型：
--
作者：
Abdelalim, Essam Mohamed;Tooyama, Ikuo
最近的研究报道了p53在DNA损伤后抑制胚胎干（ES）细胞的多能性和阻断体细胞重编程为诱导多能干（iPS）细胞中的作用。然而，迄今为止还没有证据支持p53在非应激ES细胞中的功能。在这项研究中，我们研究了pifithrin（PFT）-α，p53依赖性转录激活的抑制剂，对ES细胞自我更新的影响。我们的研究结果表明，用PFT-α处理ES细胞导致以剂量依赖性方式抑制ES细胞增殖，如细胞数量和集落大小的显著减少所示。此外，PFT-α导致细胞周期停滞和DNA合成显著减少。此外，抑制p53活性降低了细胞周期蛋白D1和Nanog的表达水平。这些发现表明，p53通路在ES细胞，而不是作为一个失活的基因，是必需的ES细胞增殖和自我更新在无应激条件下。(C)2012 Elsevier Inc. All rights reserved.
Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-alpha, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-alpha resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-alpha caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions. (C) 2012 Elsevier Inc. All rights reserved.