High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity

被引：216

作者：

Narva, Elisa ^{[1
,2
]}

Autio, Reija ^{[1
,2
,3
]}

Rahkonen, Nelly ^{[1
,2
]}

Kong, Lingjia ^{[3
]}

Harrison, Neil ^{[4
,5
]}

Kitsberg, Danny ^{[6
]}

Borghese, Lodovica ^{[7
,8
]}

Itskovitz-Eldor, Joseph ^{[9
,10
]}

Rasool, Omid ^{[1
,2
]}

Dvorak, Petr ^{[11
,12
]}

Hovatta, Outi ^{[13
]}

Otonkoski, Timo ^{[14
,15
]}

Tuuri, Timo ^{[14
]}

Cui, Wei ^{[16
]}

Brustle, Oliver ^{[7
,8
]}

Baker, Duncan ^{[17
]}

Maltby, Edna ^{[17
]}

Moore, Harry D. ^{[4
,18
]}

Benvenisty, Nissim ^{[19
]}

Andrews, Peter W. ^{[4
,5
]}

Yli-Harja, Olli ^{[3
,20
]}

Lahesmaa, Riitta ^{[1
,2
]}

机构：

[1] Univ Turku, Turku Ctr Biotechnol, Turku, Finland

[2] Abo Akad Univ, Turku, Finland

[3] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland

[4] Univ Sheffield, Ctr Stem Cell Biol, Sheffield, S Yorkshire, England

[5] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[6] Stem Cell Technol Ltd, Jerusalem, Israel

[7] Univ Bonn, Inst Reconstruct Neurobiol, Life & Brain Ctr, D-5300 Bonn, Germany

[8] Hertie Fdn, Bonn, Germany

[9] Technion Israel Inst Technol, Fac Med, Haifa, Israel

[10] Rambam Med Ctr, Dept Obstet & Gynecol, IL-31096 Haifa, Israel

[11] Masaryk Univ, Dept Biol, Fac Med, Brno, Czech Republic

[12] Acad Sci Czech Republ, Dept Mol Embryol, Inst Expt Med, Brno, Czech Republic

[13] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept CLINTEC, Stockholm, Sweden

[14] Univ Helsinki, Program Mol Neurol, Biomedicum Stem Cell Ctr, Helsinki, Finland

[15] Univ Helsinki, Childrens Hosp, Helsinki, Finland

[16] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, Fac Med, London, England

[17] Sheffield Childrens NHS Trust, Sheffield Diagnost Genet Serv, Sheffield, S Yorkshire, England

[18] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England

[19] Hebrew Univ Jerusalem, Dept Genet, Stem Cell Unit, Inst Life Sci, IL-91904 Jerusalem, Israel

[20] Inst Syst Biol, Seattle, WA USA

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 04期

基金：

英国医学研究理事会; 芬兰科学院;

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; ES CELLS; EXPRESSION; ARRAY; CHROMOSOME-16; POLYMORPHISM; INSTABILITY; CARCINOMA;

D O I：

10.1038/nbt.1615

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected.

引用

页码：371 / U103

页数：9

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