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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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.

Original languageAmerican English
Article number4825
JournalNature Communications
StatePublished - 2014

Bibliographical note

Funding Information:
We thank Batsheva Kerem, Noa Lamm and Ido Sagi for critically reading the manuscript, and Ofra Yanuka for her assistance with cell culture. N.B. is the Herbert Cohn Chair in Cancer Research. This work was supported by the Israel Science Foundation (grant no. 269/12). U.B.-D. was supported by a Clore Fellowship.

Publisher Copyright:
© 2014 Macmillan Publishers Limited.


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