Characterization of human embryonic stem cells with features of neoplastic progression.
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.
Werbowetski-Ogilvie
Tamra E
TE
Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, MDCL 5029, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Bossé
Marc
M
Stewart
Morag
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Schnerch
Angelique
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Ramos-Mejia
Veronica
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Rouleau
Anne
A
Wynder
Tracy
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Smith
Mary-Jo
MJ
Dingwall
Steve
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Carter
Tim
T
Williams
Christopher
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Harris
Charles
C
Dolling
Joanna
J
Wynder
Christopher
C
Boreham
Doug
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Bhatia
Mickie
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D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D003582:Cytogenetics; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005821:Genetic Techniques; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism
D016222:Fibroblast Growth Factor 2