Identification and classification of chromosomal aberrations in human induced pluripotent stem cells

Yoav Mayshar, Uri Ben-David, Neta Lavon, Juan Carlos Biancotti, Benjamin Yakir, Amander T. Clark, Kathrin Plath, William E. Lowry, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

620 Scopus citations

Abstract

Because of their somatic cell origin, human induced pluripotent stem cells (HiPSCs) are assumed to carry a normal diploid genome, and adaptive chromosomal aberrations have not been fully evaluated. Here, we analyzed the chromosomal integrity of 66 HiPSC and 38 human embryonic stem cell (HESC) samples from 18 different studies by global gene expression meta-analysis. We report identification of a substantial number of cell lines carrying full and partial chromosomal aberrations, half of which were validated at the DNA level. Several aberrations resulted from culture adaptation, and others are suspected to originate from the parent somatic cell. Our classification revealed a third type of aneuploidy already evident in early passage HiPSCs, suggesting considerable selective pressure during the reprogramming process. The analysis indicated high incidence of chromosome 12 duplications, resulting in significant enrichment for cell cycle-related genes. Such aneuploidy may limit the differentiation capacity and increase the tumorigenicity of HiPSCs.

Original languageAmerican English
Pages (from-to)521-531
Number of pages11
JournalCell Stem Cell
Volume7
Issue number4
DOIs
StatePublished - 8 Oct 2010

Bibliographical note

Funding Information:
We would like to thank Tamar Golan-Lev for excellent technical assistance, Dr. Danny Kitzberg for critically reading this manuscript and Dr. Sagiv Shifman for stimulating discussions. N.B. is the Herbert Cohn Chair in Cancer Research. This research was partially supported by funds from the European Community (ESTOOLS, Grant number 018739) and by funds from the Morasha-ISF (Grant number 943/09). We gratefully acknowledge support for this project provided by a grant from the Legacy Heritage Fund of New York.

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