Elevated Coding Mutation Rate During the Reprogramming of Human Somatic Cells into Induced Pluripotent Stem Cells

被引：150

作者：

Ji, Junfeng ^{[1
]}

Ng, Siemon H. ^{[1
]}

Sharma, Vivek ^{[1
]}

Neculai, Dante ^{[1
]}

Hussein, Samer ^{[2
]}

Sam, Michelle ^{[1
]}

Quang Trinh ^{[1
]}

Church, George M. ^{[3
]}

Mcpherson, John D. ^{[1
]}

Nagy, Andras ^{[2
]}

Batada, Nizar N. ^{[1
]}

机构：

[1] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada

[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

来源：

STEM CELLS | 2012年 / 30卷 / 03期

关键词：

Induced pluripotent stem cells; Stem cells; Reprogramming; Mutations; Genome instability; Exome sequencing; COPY NUMBER; GENERATION;

D O I：

10.1002/stem.1011

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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

引用

页码：435 / 440

页数：6

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