Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation
Journal Title
Nature Communications
Publication Type
Research article
Abstract
Reprogramming of somatic cells into induced Pluripotent Stem Cells (iPSCs) is a major leap towards personalised approaches to disease modelling and cell-replacement therapies. However, we still lack the ability to fully control the epigenetic status of iPSCs, which is a major hurdle for their downstream applications. Epigenetic fidelity can be tracked by genomic imprinting, a phenomenon dependent on DNA methylation, which is frequently perturbed in iPSCs by yet unknown reasons. To try to understand the causes underlying these defects, we conducted a thorough imprinting analysis using IMPLICON, a high-throughput method measuring DNA methylation levels, in multiple female and male murine iPSC lines generated under different experimental conditions. Our results show that imprinting defects are remarkably common in iPSCs, but their nature depends on the sex of donor cells and their response to culture conditions. Imprints in female iPSCs resist the initial genome-wide DNA demethylation wave during reprogramming, but ultimately cells accumulate hypomethylation defects irrespective of culture medium formulations. In contrast, imprinting defects on male iPSCs depends on the experimental conditions and arise during reprogramming, being mitigated by the addition of vitamin C (VitC). Our findings are fundamental to further optimise reprogramming strategies and generate iPSCs with a stable epigenome.
Keywords
Animals; Ascorbic Acid/metabolism; DNA Methylation; Female; Genome; Genomic Imprinting; *Induced Pluripotent Stem Cells/metabolism; Male; Mice
Department(s)
Laboratory Research
PubMed ID
36114205
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-022-33013-5
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2024-09-26 05:45:15
Last Modified: 2024-09-26 05:48:04

© 2024 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙