Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells.
Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells.
复制标题
将不完全重编程与小鼠胚胎癌细胞来源的多能干细胞的多能性提高联系起来
DOI：
10.1371/journal.pone.0010320
复制
发表时间：
2010-04-26
期刊：
影响因子：
3.7
通讯作者：
Gao S
中科院分区：
文献类型：
--
作者：
Chang G;Miao YL;Zhang Y;Liu S;Kou Z;Ding J;Chen DY;Sun QY;Gao S
体细胞核移植（Somatic cell nuclear transfer，SCNT）已被证明能够将各种分化的体细胞重编程为多能干细胞。最近，诱导多能干细胞（iPS）已成功地从小鼠和人类体细胞的过度表达的转录因子的组合。然而，由SCNT或iPS方法介导的重编程的分子机制知之甚少。越来越多的证据表明，许多肿瘤途径在iPS细胞的衍生中发挥作用。胚胎癌（EC）细胞具有干细胞和癌细胞的特性，因此它们可能是阐明重编程过程细节的更好候选者。尽管先前的研究表明EC细胞不能被重编程为真实的多能干细胞，但其原因仍不清楚。在此，将来自小鼠EC细胞（P19）的细胞核移植到去核卵母细胞中，随后建立了多能干细胞（P19 NTES细胞）。有趣的是，与单独的EC细胞相比，P19 NTES细胞延长了四倍体聚集胚胎的发育。更重要的是，我们发现印迹H19基因的表达恢复依赖于差异甲基化区域（DMR）的甲基化状态。然而，Nanog表达的诱导与P19 NTES细胞中启动子区DNA甲基化状态无关。全基因组转录组分析进一步证明P19 NTES细胞确实是P19细胞和ES细胞之间的中间体，并且发现了许多可能导致P19细胞重编程失败的有趣基因。据我们所知，我们第一次将不完全重编程与EC细胞衍生的多能干细胞的多能性改善联系起来。我们发现的候选基因可能不仅有助于理解重编程的机制，而且有助于破译肿瘤发生和多能性之间的转变。
Somatic cell nuclear transfer (SCNT) has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS) have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC) cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19) were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells) were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR). The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the transition between tumorigenesis and pluripotency.
登录
查看更多内容
影响因子：
23.9
作者：
Ko, Kinarm;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.
影响因子：
10.5
作者：
Hochedlinger, K;Blelloch, R;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
64.8
作者：
Eggan, E;Baldwin, K;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
64.8
作者：
BARTOLOMEI, MS;ZEMEL, S;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
细胞的影响转移到小鼠胚泡中对随后的发育。
影响因子：
15.3
作者：
Brinster, R L
通讯作者：
Brinster, R L