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

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

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)435-440
Number of pages6
JournalStem Cells
Volume30
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Mutation Rate
Mutation
Exome
Foreskin
Oncogenes
Point Mutation
Cell Culture Techniques
Fibroblasts
Maintenance

Keywords

  • Exome sequencing
  • Genome instability
  • Induced pluripotent stem cells
  • Mutations
  • Reprogramming
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Ji, J., Ng, S., Sharma, V., Neculai, D., Hussein, S., Sam, M., ... Batada, N. N. (2012). Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. Stem Cells, 30(3), 435-440. https://doi.org/10.1002/stem.1011

Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. / Ji, Junfeng; Ng, Siemon; Sharma, Vivek; Neculai, Dante; Hussein, Samer; Sam, Michelle; Trinh, Quang; Church, George M.; Mcpherson, John Douglas; Nagy, Andras; Batada, Nizar N.

In: Stem Cells, Vol. 30, No. 3, 03.2012, p. 435-440.

Research output: Contribution to journalArticle

Ji, J, Ng, S, Sharma, V, Neculai, D, Hussein, S, Sam, M, Trinh, Q, Church, GM, Mcpherson, JD, Nagy, A & Batada, NN 2012, 'Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells', Stem Cells, vol. 30, no. 3, pp. 435-440. https://doi.org/10.1002/stem.1011
Ji, Junfeng ; Ng, Siemon ; Sharma, Vivek ; Neculai, Dante ; Hussein, Samer ; Sam, Michelle ; Trinh, Quang ; Church, George M. ; Mcpherson, John Douglas ; Nagy, Andras ; Batada, Nizar N. / Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells. In: Stem Cells. 2012 ; Vol. 30, No. 3. pp. 435-440.
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