کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2093710 | 1081974 | 2015 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line](/preview/png/2093710.png)
• Spontaneous reversion of an ATM mutation was found in A-T iPSC
• Reversion was due to gene correction, based on LOH of a nearby SNP
• Gene expression changes between individuals overwhelm those from single mutations
• Loss of ATM in unstimulated cells primarily reduced the p53 pathway
SummaryA spontaneously reverted iPSC line was identified from an A-T subject with heterozygous ATM truncation mutations. The reverted iPSC line expressed ATM protein and was capable of radiation-induced phosphorylation of CHK2 and H2A.X. Genome-wide SNP analysis confirmed a match to source T cells and also to a distinct, non-reverted iPSC line from the same subject. Rearranged T cell receptor sequences predict that the iPSC culture originated as several independently reprogrammed cells that resolved into a single major clone, suggesting that gene correction likely occurred early in the reprogramming process. Gene expression analysis comparing ATM−/− iPSC lines to unrelated ATM+/− cells identifies a large number of differences, but comparing only the isogenic pair of A-T iPSC lines reveals that the primary pathway affected by loss of ATM is a diminished expression of p53-related mRNAs. Gene reversion in culture, although likely a rare event, provided a novel, reverted cell line for studying ATM function.
Journal: - Volume 5, Issue 6, 8 December 2015, Pages 1097–1108