title: Identification and classification of chromosomal aberrations in human induced pluripotent stem cells.
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.
authors.affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Mayshar
authors.forename: Uri
authors.initials: U
authors.lastname: Ben-David
authors.forename: Neta
authors.initials: N
authors.lastname: Lavon
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Biancotti
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yakir
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
authors.forename: Kathrin
authors.initials: K
authors.lastname: Plath
authors.forename: William E
authors.initials: WE
authors.lastname: Lowry
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000145:classification; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells