1. Copy number variation and selection during reprogramming to pluripotency
- Author
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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, and Otonkoski, Timo
- Subjects
Stem cells -- Models -- Methods -- Genetic aspects ,Cell differentiation -- Methods -- Models -- Genetic aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
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., Reprogramming somatic cells to pluripotency can be achieved by forced expression of a defined set of factors (1,2). Several methods have been developed for generating human iPS cells, such as [...]
- Published
- 2011
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