Elevated Coding Mutation Rate During the Reprogramming of Human Somatic Cells into Induced Pluripotent Stem Cells123. (14th February 2012)

• Record Type: Journal Article
• Authors: Ji, Junfeng; Ng, Siemon H.; Sharma, Vivek; Neculai, Dante; Hussein, Samer; Sam, Michelle; Trinh, Quang; Church, George M.; Mcpherson, John D.; Nagy, Andras; Batada, Nizar N.
• Is Part Of: Stem cells. Volume 30:Number 3(2012)
• Page Start: 435
• Page End: 440
• Publication Date: 2012-02-14
• Subjects: Induced pluripotent stem cells -- Stem cells -- Reprogramming -- Mutations -- Genome instability -- Exome sequencing; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1011
• Languages: English
• ISSNs: 1066-5099

Abstract

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. STEM CELLS 2012;30:435–440