Abstract
A 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.
Original language | English (US) |
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Pages (from-to) | 1097-1108 |
Number of pages | 12 |
Journal | Stem Cell Reports |
Volume | 5 |
Issue number | 6 |
DOIs | |
State | Published - Dec 8 2015 |
ASJC Scopus subject areas
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology