Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2011 Jan 27;6(1):e16478. doi: 10.1371/journal.pone.0016478.
Pluripotent stem cells (PSCs) hold significant promise in regenerative medicine due to their unlimited capacity for self-renewal and potential to differentiate into every cell type in the body. One major barrier to the use of PSCs is their potential risk for tumor initiation following differentiation and transplantation in vivo. In the current study we sought to evaluate the role of the tumor suppressor Pten in murine PSC neoplastic progression. Using eight functional assays that have previously been used to indicate PSC adaptation or transformation, Pten null embryonic stem cells (ESCs) failed to rate as significant in five of them. Instead, our data demonstrate that the loss of Pten causes the emergence of a small number of aggressive, teratoma-initiating embryonic carcinoma cells (ECCs) during differentiation in vitro, while the remaining 90-95% of differentiated cells are non-tumorigenic. Furthermore, our data show that the mechanism by which Pten null ECCs emerge in vitro and cause tumors in vivo is through increased survival and self-renewal, due to failed repression of the transcription factor Nanog.
多能干细胞（PSCs）由于其无限的自我更新能力和分化为体内每一种细胞类型的潜力，在再生医学中具有重要的应用前景。PSCs 的一个主要应用障碍是其在体内分化和移植后潜在的肿瘤起始风险。在本研究中，我们试图评估肿瘤抑制因子 Pten 在小鼠 PSC 肿瘤发生中的作用。使用之前用于指示 PSC 适应或转化的八项功能测定，Pten 缺失胚胎干细胞（ESCs）在其中五项中未能显著评分。相反，我们的数据表明，Pten 的缺失导致在体外分化过程中出现少量侵袭性、致瘤性胚胎癌细胞（ECCs），而剩余的 90-95%分化细胞是非致瘤性的。此外，我们的数据表明，Pten 缺失的 ECCs 在体外出现并在体内引起肿瘤的机制是由于转录因子 Nanog 的抑制失败导致存活和自我更新增加。
