Abstract
Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced 'stemness'. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor-initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization reveals an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells.
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Acknowledgements
This work was funded by the Canadian Institute of Health Research, the National Cancer Institute of Canada (NCIC), Ontario Institute of Cancer Research (OICR) and the Canadian Cancer Society (CCS). A fellowship from the NCIC supports T.E.W.-O. and support to M.B. from the Canada Research Chair Program. In addition, thanks to Jiabi Yang for technical support in scoring teratoma formation assays and members of the Stem Cell and Cancer Research Institute for helpful insights during the writing of the manuscript.
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T.E.W.-O. performed and designed experiments, analyzed data and assisted in writing the manuscript. M.B., M.S., V.R.-M., A.R., T.W., S.D., T.C., C.W. (from PerkinElmer) and C.H. performed experiments. A.S. analyzed bioinformatics data, and M.-J.S. conducted histological analysis. J.D., C.W. (from McMaster) and D.B. were collaborators on the paper. M.B. designed experiments, interpreted and assisted in writing the manuscript.
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Werbowetski-Ogilvie, T., Bossé, M., Stewart, M. et al. Characterization of human embryonic stem cells with features of neoplastic progression. Nat Biotechnol 27, 91–97 (2009). https://doi.org/10.1038/nbt.1516
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DOI: https://doi.org/10.1038/nbt.1516
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