Aneuploidy in pluripotent stem cells and implications for cancerous transformation.
Aneuploidy in pluripotent stem cells and implications for cancerous transformation.
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多能干细胞的非整倍性及其对癌变的影响。
DOI：
10.1007/s13238-014-0073-9
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发表时间：
2014
期刊：
影响因子：
21.1
通讯作者：
Barbaric, Ivana
中科院分区：
文献类型：
--
作者：
Na, Jie;Baker, Duncan;Zhang, Jing;Andrews, Peter W.;Barbaric, Ivana
由于一组独特的属性，人类多能干细胞（hPSC）已成为再生医学，疾病建模和药物发现的有前途的细胞来源。在长期维持hPSC的过程中确保遗传稳定性是这一奋进的关键，但hPSC可以通过获得非随机的遗传变化来适应培养物中的生活，这些遗传变化使它们更健壮且更容易生长。在单独的研究中，发现12.5%至34%的hPSC系随时间获得染色体异常，发生率随传代次数增加。在hPSC系中发现的主要遗传变化涉及染色体数目和结构（特别是染色体1、12、17和20）的变化，这让人想起在癌细胞中观察到的变化。在这篇综述中，我们总结了目前对hPSC中非整倍体的原因和后果的认识，并强调了与人类癌症和早期胚胎中观察到的遗传变化的潜在联系。我们指出，需要全面表征的机制，支持收购染色体异常和选择压力，这使得突变，坚持在hPSC文化。阐明这些机制将有助于设计最大限度地减少非整倍体hPSC出现的培养条件。此外，hPSC中的非整倍性可以提供一个独特的平台来分析可能最终导致癌症转化的基因组进化背后的驱动力。
Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation.
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2001 年 8 月 9 日之前提取的三种人类胚胎干细胞系的核型稳定性、基因分型、分化、无饲养维持和基因表达取样
影响因子：
4
作者：
Brimble, SN;Zeng, XM;Schulz, TC
通讯作者：
Schulz, TC
影响因子：
46.9
作者：
Blum, Barak;Bar-Nur, Ori;Benvenisty, Nissim
通讯作者：
Benvenisty, Nissim
影响因子：
5.6
作者：
Becker, Klaus A.;Ghule, Prachi N.;Stein, Gary S.
通讯作者：
Stein, Gary S.
影响因子：
3.5
作者：
Enver, T;Soneji, S;Andrews, PW
通讯作者：
Andrews, PW
影响因子：
5.9
作者：
Avery, Stuart;Hirst, Adam J.;Baker, Duncan;Lim, Chin Yan;Alagaratnam, Sharmini;Skotheim, Rolf I.;Lothe, Ragnhild A.;Pera, Martin F.;Colman, Alan;Robson, Paul;Andrews, Peter W.;Knowles, Barbara B.
通讯作者：
Knowles, Barbara B.