The anti-apoptotic gene survivin contributes to teratoma formation by human embryonic stem cells
The anti-apoptotic gene survivin contributes to teratoma formation by human embryonic stem cells
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DOI：
10.1038/nbt.1527
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发表时间：
2009-03-01
影响因子：
46.9
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
--
作者：
Blum, Barak;Bar-Nur, Ori;Benvenisty, Nissim
来源于人胚胎干（hES）细胞的畸胎瘤是致癌现象中的独特之处，因为它们是多克隆的，并且从明显正常的细胞发育而来（1，2）。对这一过程的更深入理解有助于开发更安全的细胞疗法，并可能有助于阐明肿瘤发生的基本原理。我们发现，从四个独立的细胞系二倍体胚胎干细胞移植产生良性畸胎瘤，没有恶性肿瘤或持续胚胎癌样细胞的迹象。相比之下，小鼠胚胎干细胞（mES）从四个细胞系一致产生恶性畸胎癌。整体基因表达分析表明，生存素（BIRC 5），一个抗凋亡的癌胚基因，是高表达的hES细胞和畸胎瘤，但不是在胚状体。生存素的遗传和药理学消融在体外和体内诱导hES细胞和畸胎瘤的凋亡。我们认为生存素在体内分化后的持续表达可能有助于hES细胞形成畸胎瘤。
Teratomas derived from human embryonic stem (hES) cells are unique among oncogenic phenomena as they are polyclonal and develop from apparently normal cells(1,2). A deeper understanding of this process should aid in the development of safer cell therapies and may help elucidate the basic principles of tumor initiation. We find that transplantation of diploid hES cells from four independent cell lines generates benign teratomas with no sign of malignancy or persisting embryonal carcinoma-like cells. In contrast, mouse embryonic stem (mES) cells from four cell lines consistently generate malignant teratocarcinomas. Global gene expression analysis shows that survivin (BIRC5), an anti-apoptotic oncofetal gene, is highly expressed in hES cells and teratomas but not in embryoid bodies. Genetic and pharmacological ablation of survivin induces apoptosis in hES cells and in teratomas both in vitro and in vivo. We suggest that continued expression of survivin upon differentiation in vivo may contribute to teratoma formation by hES cells.