Adaptation to culture of human embryonic stem cells and oncogenesis in vivo
Adaptation to culture of human embryonic stem cells and oncogenesis in vivo
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DOI：
10.1038/nbt1285
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发表时间：
2007-02-01
影响因子：
46.9
通讯作者：
Andrews, Peter W.
中科院分区：
文献类型：
--
作者：
Baker, Duncan E. C.;Harrison, Neil J.;Andrews, Peter W.
应用人类胚胎干细胞（HESC）为再生医学提供分化的细胞将需要在培养中长期持续维持未分化的干细胞。然而，不能保证延长传代期间的染色体稳定性，因为最近的HESC细胞遗传学研究显示核型畸变。观察到的核型畸变可能反映了自我更新细胞对其培养条件的渐进适应。增加细胞增殖能力的遗传变化与恶性转化有明显的相似之处，我们认为在培养的HESC中观察到的变化反映了体内发生的致瘤事件，特别是睾丸生殖细胞肿瘤。进一步支持培养适应和恶性肿瘤之间的联系，我们已经观察到在一个HESC系中形成染色体均质染色区域，这是一种几乎是癌细胞标志的遗传特征。因此，鉴定培养适应的关键基因可能揭示体外干细胞维持和体内生殖细胞肿瘤发生的关键参与者。
The application of human embryonic stem cells ( HESCs) to provide differentiated cells for regenerative medicine will require the continuous maintenance of the undifferentiated stem cells for long periods in culture. However, chromosomal stability during extended passaging cannot be guaranteed, as recent cytogenetic studies of HESCs have shown karyotypic aberrations. The observed karyotypic aberrations probably reflect the progressive adaptation of self-renewing cells to their culture conditions. Genetic change that increases the capacity of cells to proliferate has obvious parallels with malignant transformation, and we propose that the changes observed in HESCs in culture reflect tumorigenic events that occur in vivo, particularly in testicular germ cell tumors. Further supporting a link between culture adaptation and malignancy, we have observed the formation of a chromosomal homogeneous staining region in one HESC line, a genetic feature almost a hallmark of cancer cells. Identifying the genes critical for culture adaptation may thus reveal key players for both stem cell maintenance in vitro and germ cell tumorigenesis in vivo.