| Copy number variation and selection during reprogramming to pluripotency. | |
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MedLine Citation:
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PMID: 21368824 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nature Volume: 471 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-03 Completed Date: 2011-03-21 Revised Date: 2011-05-24 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 58-62 Citation Subset: IM |
Affiliation:
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Samuel Lunenfeld Research Institute, Toronto, Ontario M5T 3H7, Canada. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE26173 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Chromosome Fragile Sites / genetics DNA Copy Number Variations / genetics* Embryonic Stem Cells / cytology, metabolism Fibroblasts / cytology, metabolism Haplotypes / genetics Humans In Situ Hybridization, Fluorescence Induced Pluripotent Stem Cells / cytology, metabolism*, pathology Mosaicism Mutagenesis / genetics Nuclear Reprogramming / genetics* Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide / genetics Selection, Genetic* / genetics |
| Comments/Corrections | |
Comment In:
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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 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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