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

8Citations
Citations of this article
8Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Lin, L., Swerdel, M. R., Lazaropoulos, M. P., Hoffman, G. S., Toro-Ramos, A. J., Wright, J., … Hart, R. P. (2015). Spontaneous ATM Gene Reversion in A-T iPSC to Produce an Isogenic Cell Line. Stem Cell Reports, 5(6), 1097–1108. https://doi.org/10.1016/j.stemcr.2015.10.010

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free