ERas Is Expressed in Primate Embryonic Stem Cells But Not Related to Tumorigenesis
ERas Is Expressed in Primate Embryonic Stem Cells But Not Related to Tumorigenesis
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DOI：
10.3727/096368909788809794
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Hanazono, Yutaka
中科院分区：
文献类型：
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作者：
Tanaka, Yujiro;Ikeda, Tamako;Hanazono, Yutaka
ERas基因促进小鼠胚胎干（ES）细胞的增殖和畸胎瘤的形成。然而，它的人直系同源物在人ES细胞中不表达。这意味着移植的小鼠ES细胞的行为不能准确反映移植的人ES细胞的行为，并且使用非人灵长类动物模型可能更适合于证明基于人ES细胞的治疗的安全性。然而，ER as基因的表达尚未在非人灵长类动物ES细胞中进行检测。在这项研究中，我们克隆了食蟹猴同源物，并表明ER as基因在食蟹猴ES细胞中表达。值得注意的是，它也在食蟹猴ES细胞衍生的分化后代以及食蟹猴成体组织中表达。ERas蛋白在各种食蟹猴组织中可检测到，其通过免疫组织化学评估。食蟹猴ES细胞衍生的畸胎瘤细胞也以高于未分化的食蟹猴ES细胞的水平表达ERas基因，其在NOD/Shi-scid，IL-2 R γ（null）（NOG）小鼠中未发生肿瘤。即使当ERas基因在食蟹猴基质细胞中过表达时，也仅提高了平板接种效率，而没有促进增殖。因此，ERas不太可能促进食蟹猴细胞的致瘤性。因此，食蟹猴ES细胞比小鼠ES细胞更类似于人，尽管ER as在食蟹猴和小鼠ES细胞中表达，但在人ES细胞中不表达。
The ERas gene promotes the proliferation of and formation of teratomas by Mouse embryonic stem (ES) cells. However, its human orthologue is not expressed in human ES cells. This implies that the behavior of transplanted mouse ES cells would not accurately reflect the behavior of transplanted human ES cells and that the use of nonhuman primate models might be more appropriate to demonstrate the safety of human ES cell-based therapies. However, the expression of the ERas gene has not been examined in nonhuman primate ES cells. In this study, we cloned the cynomolgus homologue and showed that the ERas gene is expressed in cynomolgus ES cells. Notably, it is also expressed in cynomolgus ES cell-derived differentiated progeny as well as cynomolgus adult tissues. The ERas protein is detectable in various cynomolgus tissues its assessed by immunohistochemisty. Cynomolgus ES cell-derived teratoma cells, which also expressed the ERas gene at higher levels than the undifferentiated cynomolgus ES cells, did not develop tumors in NOD/Shi-scid, IL-2R gamma(null) (NOG) mice. Even when the ERas gene was overexpressed in cynomolgus stromal cells, only the plating efficiency was improved and the proliferation was not promoted. Thus, it is unlikely that ERas contributes to the tumorigenicity of cynomolgus cells. Therefore, cynomolgus ES cells are more similar to human than mouse ES cells despite that ERas is expressed in cynomolgus and mouse ES cells but not in human ES cells.