Title: Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line.

Authors: Lin, Lucy; Swerdel, Mavis R; Lazaropoulos, Michael P; Hoffman, Gary S; Toro-Ramos, Alana J; Wright, Jennifer; Lederman, Howard; Chen, Jianmin; Moore, Jennifer C; Hart, Ronald P

Published In Stem Cell Reports, (2015 Dec 08)

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.

PubMed ID: 26677768

MeSH Terms: No MeSH terms associated with this publication