Reprogramming p53-Deficient Germline Stem Cells Into Pluripotent State by Nanog
Reprogramming p53-Deficient Germline Stem Cells Into Pluripotent State by Nanog
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Nanog 将 p53 缺陷的生殖干细胞重编程为多能状态
DOI：
10.1089/scd.2018.0047
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发表时间：
2018-05-09
影响因子：
4
通讯作者：
Han, Chunsheng
中科院分区：
文献类型：
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作者：
Feng, Yanmin;Ning, Yan;Han, Chunsheng
培养的小鼠精原干细胞（SSCs），也称为种系干细胞（GSCs），可以自发地或经过基因修饰后恢复到多能状态。然而，重编程的效率很低，其潜在的机制仍然知之甚少。在本研究中，我们进行了转录组学分析，发现许多转录因子和表观遗传修饰因子在GSCs和胚胎干细胞之间存在差异表达。我们使用Yamanaka 4因子将GSCs重编程为多能状态失败，但当Nanog和Ted加入时成功了。更重要的是，Nanog在p53缺失的GSC细胞系中也实现了重编程，效率为0.02%。尽管嵌合体形成率较低，但这些gsc诱导的多能干细胞具有体外和体内分化能力，这可能是由于某些父本印迹基因甲基化异常引起的。总之，这些结果表明，GSC可以通过多种途径被重编程为多能状态，并有助于我们理解GSC重编程的机制
Cultured mouse spermatogonial stem cells (SSCs), also known as germline stem cells (GSCs), revert back to pluripotent state either spontaneously or upon being modified genetically. However, the reprogramming efficiencies are low, and the underlying mechanism remains poorly understood. In the present study, we conducted transcriptomic analysis and found that many transcription factors and epigenetic modifiers were differentially expressed between GSCs and embryonic stem cells. We failed in reprogramming GSCs to pluripotent state using the Yamanaka 4 Factors, but succeeded when Nanog and Ted were included. More importantly, reprogramming was also achieved with Nanog alone in a p53-deficient GSC line with an efficiency of 0.02 parts per thousand. These GSC-derived-induced pluripotent stem cells possessed in vitro and in vivo differentiation abilities despite the low rate of chimera formation, which might be caused by abnormal methylation in certain paternally imprinted genes. Together, these results show that GSCs can be reprogrammed to pluripotent state via multiple avenues and contribute to our understanding of the mechanisms of GSC reprogramming