Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells

Junfeng Ji, Siemon H Ng, Vivek Sharma, Dante Neculai, Samer Hussein, Michelle Sam, Quang Trinh, George M Church, John D McPherson, Andras Nagy, Nizar N Batada

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Mutations in human induced pluripotent stem cells (iPSCs) pose a risk for their clinical use due to preferential reprogramming of mutated founder cell and selection of mutations during maintenance of iPSCs in cell culture. It is unknown, however, if mutations in iPSCs are due to stress associated with oncogene expression during reprogramming. We performed whole exome sequencing of human foreskin fibroblasts and their derived iPSCs at two different passages. We found that in vitro passaging contributed 7% to the iPSC coding point mutation load, and ultradeep amplicon sequencing revealed that 19% of the mutations preexist as rare mutations in the parental fibroblasts suggesting that the remaining 74% of the mutations were acquired during cellular reprogramming. Simulation suggests that the mutation intensity during reprogramming is ninefold higher than the background mutation rate in culture. Thus the factor induced reprogramming stress contributes to a significant proportion of the mutation load of iPSCs.

Original languageEnglish
Pages (from-to)435-40
Number of pages6
Issue number3
Publication statusPublished - Mar 2012

Keywords / Materials (for Non-textual outputs)

  • Cell Dedifferentiation
  • Cells, Cultured
  • DNA Mutational Analysis
  • Fibroblasts
  • Genetic Vectors
  • Humans
  • Induced Pluripotent Stem Cells
  • Kruppel-Like Transcription Factors
  • Mutagenesis
  • Octamer Transcription Factor-3
  • Open Reading Frames
  • Point Mutation
  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins
  • Retroviridae
  • SOXB1 Transcription Factors


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