Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Uri Ben-David, Gal Arad, Uri Weissbein, Berhan Mandefro, Adva Maimon, Tamar Golan-Lev, Kavita Narwani, Amander T. Clark, Peter W. Andrews, Nissim Benvenisty, Juan Carlos Biancotti

ABSTRACT

Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is trisomy of chromosome 12. Here we dissect the cellular and molecular implications of this trisomy in hPSCs. Global gene expression analyses reveal that trisomy 12 profoundly affects the gene expression profile of hPSCs, inducing a transcriptional programme similar to that of germ cell tumours. Comparison of proliferation, differentiation and apoptosis between diploid and aneuploid hPSCs shows that trisomy 12 significantly increases the proliferation rate of hPSCs, mainly as a consequence of increased replication. Furthermore, trisomy 12 increases the tumorigenicity of hPSCs in vivo, inducing transcriptionally distinct teratomas from which pluripotent cells can be recovered. Last, a chemical screen of 89 anticancer drugs discovers that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors. Together, these findings demonstrate the extensive effect of trisomy 12 and highlight its perils for successful hPSC applications. More... »

PAGES

4825

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms5825

DOI

http://dx.doi.org/10.1038/ncomms5825

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015768332

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25198699


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