Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs during Reprogramming and Time in Culture

被引：664

作者：

Laurent, Louise C. ^{[1
,3
,4
]}

Ulitsky, Igor ^{[6
,7
]}

Slavin, Ileana ^{[3
,4
]}

Tran, Ha ^{[3
,4
]}

Schork, Andrew ^{[2
]}

Morey, Robert ^{[1
,3
,4
]}

Lynch, Candace ^{[3
,4
]}

Harness, Julie V. ^{[8
]}

Lee, Sunray ^{[9
]}

Barrero, Maria J. ^{[10
,11
]}

Ku, Sherman ^{[5
]}

Martynova, Marina ^{[12
]}

Semechkin, Ruslan ^{[12
]}

Galat, Vasiliy ^{[13
,14
,15
]}

Gottesfeld, Joel ^{[5
]}

Belmonte, Juan Carlos Izpisua ^{[10
,11
]}

Murry, Chuck ^{[16
]}

Keirstead, Hans S. ^{[8
]}

Park, Hyun-Sook ^{[9
]}

Schmidt, Uli ^{[17
]}

Laslett, Andrew L. ^{[18
,19
,20
]}

Muller, Franz-Josef ^{[3
,4
]}

Nievergelt, Caroline M. ^{[2
]}

Shamir, Ron ^{[3
,4
,7
]}

Loring, Jeanne F.

机构：

[1] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[4] Scripps Res Inst, Ctr Regenerat Med, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[6] Whitehead Inst, Cambridge, MA 02142 USA

[7] Tel Aviv Univ, Dept Comp Sci, IL-69978 Tel Aviv, Israel

[8] Univ Calif Irvine, Sue & Bill Gross Stem Cell Ctr, Dept Anat & Neurobiol, Irvine, CA 92697 USA

[9] Modern Cell & Tissue Technol MCTT Inc, Seoul 139240, South Korea

[10] Salk Inst Biol Studies, La Jolla, CA 92037 USA

[11] Ctr Med Regenerat Barcelona, E-08003 Barcelona, Spain

[12] Int Stem Cell Corp, Oceanside, CA 92056 USA

[13] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

[14] Northwestern Univ, Childrens Mem Res Ctr, IPS, Chicago, IL 60614 USA

[15] Northwestern Univ, Childrens Mem Res Ctr, Human Stem Cell Core Facil, Chicago, IL 60614 USA

[16] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[17] Sydney IVF, Stem Cell Lab, Sydney, NSW 2000, Australia

[18] CSIRO, Clayton, Vic 3168, Australia

[19] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3168, Australia

[20] Australian Stem Cell Ctr, Clayton, Vic 3168, Australia

来源：

CELL STEM CELL | 2011年 / 8卷 / 01期

基金：

以色列科学基金会;

关键词：

EMBRYONIC STEM-CELLS; CHROMOSOMAL-ABNORMALITIES; LUNG-CANCER; EXPRESSION; IDENTIFICATION; AMPLIFICATION; HYBRIDIZATION; MICROARRAY; REGION; TUMORS;

D O I：

10.1016/j.stem.2010.12.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high-resolution SNP (single-nucleotide polymorphism) analysis on 186 pluripotent and 119 nonpluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to nonpluripotent samples, with variations enriched in specific genomic regions. The distribution of these variations differed between hESCs and hiPSCs, characterized by large numbers of duplications found in a few hESC samples and moderate numbers of deletions distributed across many hiPSC samples. For hiPSCs, the reprogramming process was associated with deletions of tumor-suppressor genes, whereas time in culture was associated with duplications of oncogenic genes. We also observed duplications that arose during a differentiation protocol. Our results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.

引用

页码：106 / 118

页数：13

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