Aneuploidy in pluripotent stem cells and implications for cancerous transformation

作者: Jie Na , Duncan Baker , Jing Zhang , Peter W. Andrews , Ivana Barbaric

DOI: 10.1007/S13238-014-0073-9

关键词: Induced pluripotent stem cellStem cellGeneticsHuman geneticsAneuploidyRegenerative medicineEmbryonic stem cellComputational biologyCancer cellBiologyCellular differentiation

摘要: Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance genetic stability over long term maintenance hPSCs is pivotal in this endeavor, but can adapt life culture by acquiring non-random changes that render them more robust easier grow. In separate studies between 12.5% 34% hPSC lines were found acquire chromosome abnormalities time, with the incidence increasing passage number. The predominant involve number structure (particularly chromosomes 1, 12, 17 20), reminiscent observed cancer cells. review, we summarize current knowledge on causes consequences aneuploidy highlight potential links cancers early embryos. We point need comprehensive characterization mechanisms underpinning both acquisition chromosomal selection pressures, which allow mutations persist cultures. Elucidation these will help design conditions minimize appearance aneuploid hPSCs. Moreover, may provide platform analyse driving forces behind genome evolution eventually lead cancerous transformation.

参考文章(81)
Elwin E. Fraley, David L. Bronson, Nancy Wang, Beth Trend, Nonrandom Abnormalities in Chromosome 1 in Human Testicular Cancers Cancer Research. ,vol. 40, pp. 796- 802 ,(1980)
Terry Hassold, Patricia Hunt, To err (meiotically) is human: the genesis of human aneuploidy Nature Reviews Genetics. ,vol. 2, pp. 280- 291 ,(2001) , 10.1038/35066065
Ragnhild A. Lothe, Outi Monni, Rolf I. Skotheim, Spyro Mousses, Anne Kallioniemi, Anne Kallioniemi, Olli P. Kallioniemi, Sophie D. Fosså, New insights into testicular germ cell tumorigenesis from gene expression profiling. Cancer Research. ,vol. 62, pp. 2359- 2364 ,(2002)
S. Alagaratnam, G. E. Lind, S. M. Kraggerud, R. A. Lothe, R. I. Skotheim, The testicular germ cell tumour transcriptome. International Journal of Andrology. ,vol. 34, ,(2011) , 10.1111/J.1365-2605.2011.01169.X
B McClintock, The significance of responses of the genome to challenge Science. ,vol. 226, pp. 792- 801 ,(1984) , 10.1126/SCIENCE.15739260
Seval Türkmen, Mathias Riehn, Eva Klopocki, Mara Molkentin, Richard Reinhardt, Thomas Burmeister, A BACH2-BCL2L1 fusion gene resulting from a t(6;20)(q15;q11.2) chromosomal translocation in the lymphoma cell line BLUE-1 Genes, Chromosomes and Cancer. ,vol. 50, pp. 389- 396 ,(2011) , 10.1002/GCC.20863
K. T. Jones, S. I. R. Lane, Molecular causes of aneuploidy in mammalian eggs Development. ,vol. 140, pp. 3719- 3730 ,(2013) , 10.1242/DEV.090589
Tamra E Werbowetski-Ogilvie, Marc Bossé, Morag Stewart, Angelique Schnerch, Veronica Ramos-Mejia, Anne Rouleau, Tracy Wynder, Mary-Jo Smith, Steve Dingwall, Tim Carter, Christopher Williams, Charles Harris, Joanna Dolling, Christopher Wynder, Doug Boreham, Mickie Bhatia, None, Characterization of human embryonic stem cells with features of neoplastic progression Nature Biotechnology. ,vol. 27, pp. 91- 97 ,(2009) , 10.1038/NBT.1516
Neil J Harrison, Duncan Baker, Peter W Andrews, Culture adaptation of embryonic stem cells echoes germ cell malignancy International Journal of Andrology. ,vol. 30, pp. 275- 281 ,(2007) , 10.1111/J.1365-2605.2007.00762.X
Sandii N. Brimble, Xianmin Zeng, Deborah A. Weiler, Yongquan Luo, Ying Liu, Ian G. Lyons, William J. Freed, Allan J. Robins, Mahendra S. Rao, Thomas C. Schulz, Karyotypic Stability, Genotyping, Differentiation, Feeder-Free Maintenance, and Gene Expression Sampling in Three Human Embryonic Stem Cell Lines Derived Prior to August 9, 2001 Stem Cells and Development. ,vol. 13, pp. 585- 597 ,(2004) , 10.1089/SCD.2004.13.585