Publication Date:
2011-03-04
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hussein, Samer M -- Batada, Nizar N -- Vuoristo, Sanna -- Ching, Reagan W -- Autio, Reija -- Narva, Elisa -- Ng, Siemon -- Sourour, Michel -- Hamalainen, Riikka -- Olsson, Cia -- Lundin, Karolina -- Mikkola, Milla -- Trokovic, Ras -- Peitz, Michael -- Brustle, Oliver -- Bazett-Jones, David P -- Alitalo, Kari -- Lahesmaa, Riitta -- Nagy, Andras -- Otonkoski, Timo -- England -- Nature. 2011 Mar 3;471(7336):58-62. doi: 10.1038/nature09871.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Toronto, Ontario M5T 3H7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368824" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line
;
Cellular Reprogramming/*genetics
;
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
;
Oligonucleotide Array Sequence Analysis
;
Polymorphism, Single Nucleotide/genetics
;
*Selection, Genetic/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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