期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 3, 期 6, 页码 686-691出版社
ALPHAMED PRESS
DOI: 10.5966/sctm.2013-0158
关键词
iPSCs; mRNA reprogramming; Genome integrity; SNP/CNV analysis; Hepatic differentiation
资金
- Association Francaise Contre les Myopathies
- Region Ile de France (DIM Stem Pole)
- HEMO-iPS [2011-Rare-006]
- InnovaLiv [FP7-HEALTH.2011.1.4-2-278152]
- Liv-iPS [ANR-2010-RFCS-004]
The use of synthetic messenger RNAs to generate human induced pluripotent stem cells (iPSCs) is particularly appealing for potential regenerative medicine applications, because it overcomes the common drawbacks of DNA-based or virus-based reprogramming strategies, including transgene integration in particular. We compared the genomic integrity of mRNA-derived iPSCs with that of retrovirus-derived iPSCs generated in strictly comparable conditions, by single-nucleotide polymorphism (SNP) and copy number variation (CNV) analyses. We showed that mRNA-derived iPSCs do not differ significantly from the parental fibroblasts in SNP analysis, whereas retrovirus-derived iPSCs do. We found that the number of CNVs seemed independent of the reprogramming method, instead appearing to be clone-dependent. Furthermore, differentiation studies indicated that mRNA-derived iPSCs differentiated efficiently into hepatoblasts and that these cells did not load additional CNVs during differentiation. The integration-free hepatoblasts that were generated constitute a new tool for the study of diseased hepatocytes derived from patients' iPSCs and their use in the context of stem cell-derived hepatocyte transplantation. Our findings also highlight the need to conduct careful studies on genome integrity for the selection of iPSC lines before using them for further applications.
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