胚胎干细胞（ESC）和诱导多能干细胞（iPSC）具有分化成不同细胞谱系的内在能力，这使它们成为再生医学的有力工具。尽管如此，这些干细胞在移植后产生畸胎瘤的倾向对其治疗用途构成了巨大的障碍。在之前的研究中，我们通过蛋白质组分析发现了一系列在多能状态下特异性表达的细胞表面蛋白。在这里，我们重点关注 EPHA2，这是一种在未分化的小鼠 ESC 表面大量存在的蛋白质，并且在分化时会减少。 Epha2 的敲除导致小鼠 ESC 的自发分化，强调了 EPHA2 在维持未分化细胞状态中的关键作用。进一步的研究表明，在小鼠和人类 PSC 的分化过程中，EPHA2 和 OCT4 的表达之间存在很强的相关性。值得注意的是，从小鼠 ESC 衍生的肝谱系中去除 EPHA2 细胞，将其移植到免疫缺陷小鼠体内后，可以减少肿瘤的形成。同样，在人类 iPSC 中，较大比例的 EPHA2 细胞与较高的 OCT4 表达相关，反映了在小鼠 ESC 中观察到的模式。总之，EPHA2 成为选择未分化干细胞的潜在标志物，为降低再生治疗中干细胞移植后的肿瘤发生风险提供了一种有价值的方法。© 作者 2024。由牛津大学出版社出版。

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) possess the intrinsic ability to differentiate into diverse cellular lineages, marking them as potent instruments in regenerative medicine. Nonetheless, the proclivity of these stem cells to generate teratomas post-transplantation presents a formidable obstacle to their therapeutic utility. In previous studies, we identified an array of cell surface proteins specifically expressed in the pluripotent state, as revealed through proteomic analysis. Here we focused on EPHA2, a protein found to be abundantly present on the surface of undifferentiated mouse ESCs and is diminished upon differentiation. Knock-down of Epha2 led to the spontaneous differentiation of mouse ESCs, underscoring a pivotal role of EPHA2 in maintaining an undifferentiated cell state. Further investigations revealed a strong correlation between EPHA2 and OCT4 expression during the differentiation of both mouse and human PSCs. Notably, removing EPHA2+ cells from mouse ESC-derived hepatic lineage reduced tumor formation after transplanting them into immune-deficient mice. Similarly, in human iPSCs, a larger proportion of EPHA2+ cells correlated with higher OCT4 expression, reflecting the pattern observed in mouse ESCs. Conclusively, EPHA2 emerges as a potential marker for selecting undifferentiated stem cells, providing a valuable method to decrease tumorigenesis risks after stem-cell transplantation in regenerative treatments.© The Author(s) 2024. Published by Oxford University Press.