Characterization of Human Embryonic Stem Cells with Features of Neoplastic Progression

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2009 Jan 6

PMID 19122652

Citations 118

Authors

Tamra E Werbowetski-Ogilvie

Marc Bosse

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity.

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