Document Detail

Copy number variation and selection during reprogramming to pluripotency.
MedLine Citation:
PMID:  21368824     Owner:  NLM     Status:  MEDLINE    
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.
Samer M Hussein; Nizar N Batada; Sanna Vuoristo; Reagan W Ching; Reija Autio; Elisa Närvä; Siemon Ng; Michel Sourour; Riikka Hämäläinen; Cia Olsson; Karolina Lundin; Milla Mikkola; Ras Trokovic; Michael Peitz; Oliver Brüstle; David P Bazett-Jones; Kari Alitalo; Riitta Lahesmaa; Andras Nagy; Timo Otonkoski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  471     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-03     Completed Date:  2011-03-21     Revised Date:  2011-05-24    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  58-62     Citation Subset:  IM    
Samuel Lunenfeld Research Institute, Toronto, Ontario M5T 3H7, Canada.
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MeSH Terms
Cell Line
Chromosome Fragile Sites / genetics
DNA Copy Number Variations / genetics*
Embryonic Stem Cells / cytology,  metabolism
Fibroblasts / cytology,  metabolism
Haplotypes / genetics
In Situ Hybridization, Fluorescence
Induced Pluripotent Stem Cells / cytology,  metabolism*,  pathology
Mutagenesis / genetics
Nuclear Reprogramming / genetics*
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide / genetics
Selection, Genetic* / genetics
Comment In:
Cell Stem Cell. 2011 Apr 8;8(4):347-8   [PMID:  21474093 ]
Nat Rev Cancer. 2011 Apr;11(4):232   [PMID:  21548395 ]
Nat Rev Genet. 2011 Apr;12(4):230   [PMID:  21386865 ]
Nature. 2011 Mar 3;471(7336):46-7   [PMID:  21368819 ]

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