Journal
NATURE BIOTECHNOLOGY
Volume 27, Issue 1, Pages 91-97Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1516
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Funding
- Canadian Institute of Health Research
- National Cancer Institute of Canada (NCIC)
- Ontario Institute of Cancer Research (OICR)
- Canadian Cancer Society (CCS)
- NCIC
- Canada Research Chair Program
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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. (C) 2009 Nature America, Inc. All rights reserved.
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