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

被引：583

作者：

Mayshar, Yoav ^{[1
]}

Ben-David, Uri ^{[1
]}

Lavon, Neta ^{[1
]}

Biancotti, Juan-Carlos ^{[2
]}

Yakir, Benjamin ^{[3
]}

Clark, Amander T. ^{[4
,5
]}

Plath, Kathrin ^{[5
,6
]}

Lowry, William E. ^{[4
,5
]}

Benvenisty, Nissim ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel

[2] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA

[3] Hebrew Univ Jerusalem, Dept Stat, IL-91905 Jerusalem, Israel

[4] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Broad Stem Cell Ctr, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

来源：

CELL STEM CELL | 2010年 / 7卷 / 04期

关键词：

COPY NUMBER VARIATION; COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION; CULTURE; ANEUPLOIDY; ABNORMALITIES; LEUKEMIAS; IDENTIFY; PROGRAM; REGIONS;

D O I：

10.1016/j.stem.2010.07.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 si:em 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.

引用

页码：521 / 531

页数：11

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