Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

Open Access Research article

Astrocytes derived from trisomic human embryonic stem cells express markers of astrocytic cancer cells and premalignant stem-like progenitors

Sailesh Gopalakrishna-Pillai and Linda E Iverson*

Author Affiliations

Stem Cell Biology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road, Duarte CA, 91010, USA

For all author emails, please log on.

BMC Medical Genomics 2010, 3:12  doi:10.1186/1755-8794-3-12

Published: 27 April 2010

Abstract

Background

Trisomic variants of human embryonic stem cells (hESCs) arise spontaneously in culture. Although trisomic hESCs share many properties with diploid hESCs, they also exhibit features of cancer stem cells. Since most hESC-based therapies will utilize differentiated derivatives, it is imperative to investigate the potential of trisomic hESCs to undergo malignant transformation during differentiation prior to their use in the clinical setting.

Methods

Diploid and trisomic hESCs were differentiated into astrocytic progenitors cells (APCs), RNA extracted and hybridized to human exon-specific microarrays. Global gene expression profiles of diploid and trisomic APCs were compared to that of an astrocytoma cell line and glioblastoma samples, analyzed by others, using the same microarray platform.

Results

Bioinformatic analysis of microarray data indicates that differentiated trisomic APCs exhibit global expression profiles with similarities to the malignant astrocytoma cell line. An analogous trend is observed in comparison to glioblastoma samples indicating that trisomic APCs express markers of astrocytic cancer cells. The analysis also allowed identification of transcripts predicted to be differentially expressed in brain tumor stem cells. These data indicate that in vitro differentiation of trisomic hESCs along astrocytic pathways give rise to cells exhibiting properties of premalignant astrocytic stem/progenitor cells.

Conclusions

Given their occult nature, opportunities to study premalignant stem/progenitor cells in human have been few. The ability to propagate and direct the differentiation of aneuploid hESCs provides a powerful in vitro system for investigating biological properties of human cells exhibiting features of premalignant stem cells. This in vitro culture system can be used to elucidate changes in gene expression occurring enroute to malignant transformation and to identify molecular markers of cancer stem/progenitor cells. These markers are invaluable for diagnostic purposes and may be novel targets for therapeutic intervention.