Characterization of human embryonic stem cells with features of neoplastic progression Academic Article uri icon

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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.

authors

  • Werbowetski-Ogilvie, Tamra E
  • Bossé, Marc
  • Stewart, Morag
  • Schnerch, Angelique
  • Ramos-Mejia, Veronica
  • Rouleau, Anne
  • Wynder, Tracy
  • Smith, Mary-Jo
  • Dingwall, Steve
  • Carter, Tim
  • Williams, Constance
  • Harris, Charles
  • Dolling, Joanna
  • Wynder, Christopher
  • Boreham, Doug
  • Bhatia, Mick

publication date

  • January 2009