Copy number variation and selection during reprogramming to pluripotency

被引：696

作者：

Hussein, Samer M. ^{[1
,2
]}

Batada, Nizar N. ^{[3
]}

Vuoristo, Sanna ^{[1
]}

Ching, Reagan W. ^{[4
]}

Autio, Reija ^{[5
,6
,7
]}

Narva, Elisa ^{[5
,6
]}

Ng, Siemon ^{[3
]}

Sourour, Michel ^{[2
]}

Hamalainen, Riikka ^{[1
,2
]}

Olsson, Cia ^{[1
]}

Lundin, Karolina ^{[1
]}

Mikkola, Milla ^{[1
]}

Trokovic, Ras ^{[1
]}

Peitz, Michael ^{[8
,9
]}

Bruestle, Oliver ^{[8
,9
]}

Bazett-Jones, David P. ^{[4
]}

Alitalo, Kari ^{[10
,11
]}

Lahesmaa, Riitta ^{[5
,6
]}

Nagy, Andras ^{[2
,12
]}

Otonkoski, Timo ^{[1
,13
]}

机构：

[1] Univ Helsinki, Biomedicum Stem Cell Ctr, Res Program Unit, FI-00014 Helsinki, Finland

[2] Samuel Lunenfeld Res Inst, Toronto, ON M5T 3H7, Canada

[3] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada

[4] Hosp Sick Children, Dept Genet & Genome Biol, Toronto, ON M5G 1L7, Canada

[5] Univ Turku, Turku Ctr Biotechnol, FIN-20520 Turku, Finland

[6] Abo Akad Univ, FIN-20520 Turku, Finland

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

[8] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany

[9] Hertie Fdn, D-53127 Bonn, Germany

[10] Univ Helsinki, Lab Mol Canc Biol, FI-00014 Helsinki, Finland

[11] Univ Helsinki, Cent Hosp, FI-00014 Helsinki, Finland

[12] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[13] Univ Helsinki, Childrens Hosp, FI-00029 Helsinki, Finland

来源：

NATURE | 2011年 / 471卷 / 7336期

基金：

芬兰科学院;

关键词：

EMBRYONIC STEM-CELLS; DNA-DAMAGE RESPONSE; SELF-RENEWAL; FRAGILE SITES; DIFFERENTIATION; FIBROBLASTS; SUPPRESSION; ACTIVATION; INDUCTION; CULTURE;

D O I：

10.1038/nature09871

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood. There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment. Using a high-resolution single nucleotide polymorphism array, we compared copy number variations (CNVs) of different passages of human iPS cells with their fibroblast cell origins and with human embryonic stem (ES) cells. Here we show that significantly more CNVs are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells. Most CNVs are formed de novo and generate genetic mosaicism in early-passage human iPS cells. Most of these novel CNVs rendered the affected cells at a selective disadvantage. Remarkably, expansion of human iPS cells in culture selects rapidly against mutated cells, driving the lines towards a genetic state resembling human ES cells.

引用

页码：58 / U67

页数：7

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