期刊
STEM CELLS
卷 30, 期 3, 页码 435-440出版社
WILEY
DOI: 10.1002/stem.1011
关键词
Induced pluripotent stem cells; Stem cells; Reprogramming; Mutations; Genome instability; Exome sequencing
资金
- Ontario Institute for Cancer Research through Ontario Ministry of Research and Innovation
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
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