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.
Mayshar
Yoav
Y
Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
Ben-David
Uri
U
Lavon
Neta
N
Biancotti
Juan-Carlos
JC
Yakir
Benjamin
B
Clark
Amander T
AT
Plath
Kathrin
K
Lowry
William E
WE
Benvenisty
Nissim
N
D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000145:classification; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells