Copy number variation and selection during reprogramming to pluripotency

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalNature
Volume471
Issue number7336
DOIs
Publication statusPublished - 3 Mar 2011

Keywords / Materials (for Non-textual outputs)

  • Cell Line
  • Cellular Reprogramming
  • Chromosome Fragile Sites
  • DNA Copy Number Variations
  • Embryonic Stem Cells
  • Fibroblasts
  • Haplotypes
  • Humans
  • In Situ Hybridization, Fluorescence
  • Induced Pluripotent Stem Cells
  • Mosaicism
  • Mutagenesis
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Selection, Genetic

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