Aneuploidy in pluripotent stem cells and implications for cancerous transformation

doi:10.1007/s13238-014-0073-9

Protein Cell

2014, Vol. 5

Issue (8) : 569-579 https://doi.org/10.1007/s13238-014-0073-9

REVIEW

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Jie Na¹(

), Duncan Baker², Jing Zhang¹, Peter W. Andrews³, Ivana Barbaric³(

)

¹. School of Medicine, Tsinghua University, Beijing 100084, China
². Sheffield Diagnostic Genetic Services, Sheffield Children’s Hospital, Sheffield S10 2TH, UK
³. Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield S10 2TN, UK

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Abstract

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.

Keywords human pluripotent stem cells (hPSCs) culture adaptation aneuploidy cancer genetic changes

Corresponding Author(s): Jie Na,Ivana Barbaric

Issue Date: 27 August 2014

Cite this article:

Jie Na,Duncan Baker,Jing Zhang, et al. Aneuploidy in pluripotent stem cells and implications for cancerous transformation[J]. Protein Cell, 2014, 5(8): 569-579.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-014-0073-9
https://academic.hep.com.cn/pac/EN/Y2014/V5/I8/569

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