Identification and Classification of Chromosomal Aberrations in Human Induced Pluripotent Stem Cells

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. ► Large-scale aneuploidy analysis in human iPSCs and ESCs based on gene expression data ► Classification of the origin of chromosomal aberrations in human iPSCs ► Aneuploidy in human iPS cells frequently involves chromosome 12 duplications ► Chromosome 12 duplications involve upregulation of NANOG and GDF3