| Accession | PRJCA000700 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | Increased NHEJ Downregulated the Genomic Stability of iPS | ||||||||||
| Relevance | Medical | ||||||||||
| Data types |
Whole genome sequencing
Transcriptome or Gene expression Raw sequence reads |
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| Organisms | Mus musculus | ||||||||||
| Description | Background: Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells (ESCs) in terms of their morphology, gene expression and in vitro differentiation. A recent study demonstrated that the level of genomic stability of iPSCs is lower than that of ESCs. However, the mechanism underlying the high tendency toward mutagenesis of the former cells is unknown. Methods: We treated the mouse iPSCs, mouse ESCs and mouse somatic MEF cells with 4Gy ionizing radiation (IR) to introduce DNA lesions. Four hours IR treatment, we used whole genome resequencing technology to evaluate the fidelity of DNA damage repair for each cell line. We also performed genomic stability analysis for iPS cell derived and ES cell derived mice to test their genome stability in vivo. Results: We found that iPSCs display a low level of DNA-damage repair capacity. After IR treatment, there were more somatic mutations and small indels in iPSCs than in ESCs and MEFs. The increased NHEJ DNA damage repair ability and deficient HR DNA damage repair in the iPSCs were responsible for their low genomic fidelity. Additionally, compared with ES-derived mice and C57 mice, the mice derived from iPSCs appeared a low DNA-damage repair capacity and were likely more sensitive to DNA damage. Conclusion: iPSCs were more likely to harbor genomic abnormalities. The low genomic fidelity of the DNA-damage repair in iPSCs was responsible for their genome instability and their high rate of tumorigenesis in vivo. | ||||||||||
| Sample scope | cell line | ||||||||||
| Release date | 2018-02-01 | ||||||||||
| Publication |
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| Submitter | Guochao Li (liguochao@big.ac.cn) | ||||||||||
| Organization | Beijing Institute of Genomics, Chinese Academy of Sciences | ||||||||||
| Submission date | 2018-01-23 |