TY - JOUR
T1 - Identification and classification of chromosomal aberrations in human induced pluripotent stem cells
AU - Mayshar, Yoav
AU - Ben-David, Uri
AU - Lavon, Neta
AU - Biancotti, Juan Carlos
AU - Yakir, Benjamin
AU - Clark, Amander T.
AU - Plath, Kathrin
AU - Lowry, William E.
AU - Benvenisty, Nissim
N1 - 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.
PY - 2010/10/8
Y1 - 2010/10/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957334627&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2010.07.017
DO - 10.1016/j.stem.2010.07.017
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AN - SCOPUS:77957334627
SN - 1934-5909
VL - 7
SP - 521
EP - 531
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 4
ER -