IG-DMR escapes from global hypomethylation during adult neural stem cells reprogramming [MeDIP-seq]

Genomic imprinting is an epigenetic mechanism that causes monoallelic expression of genes depending on their parental origin. Loss of imprinting (LOI) is associated with cancer progression and human imprinting disorders (IDs), impacting foetal development, metabolism and cognition. Imprinted genes, organized in clusters, rely on methylation at imprint control regions (ICRs), which are differentially methylated regions (DMRs) on both parental chromosomes. Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) is a valuable tool to understand the mechanisms associated with pluripotency and holds promise for generating patient-specific stem cells for therapeutical applications to treat different pathologies such as IDs. Here, we conduct genome-wide RNA-seq and MeDIP-seq analysis on mouse iPSCs derived from adult neural stem cells (NSCs). Our findings reveal a comprehensive alteration in iPSCs transcriptome profile, aligning with DNA hypomethylation. This correlation is pivotal in discerning which modifications in genomic imprinting during the reprogramming process represent undesirable epigenetic abnormalities that could compromise the quality of iPSCs. Simultaneously, it helps identify genuine epigenetic modifications that are inherently linked to pluripotency, thus ensuring a clearer understanding of the factors influencing iPSC quality and pluripotent potential Gene imprinting is a molecular mechanism by which the expression of a gene is limited in a parent-of-origin manner. It has been shown that methylation in imprinting control regions (ICRs) is crucial for monoallelic expression. We isolated neural stem cells (NSCs) from the sub-ventricular zone of adult mouse brains. We then reprogrammed adult NSCs to iPSCs by co-transfection of Oct4 and Klf4 plasmids in retroviral vectors. We have profiled the methylome genome-wide with Methylated DNA immunoprecipitation sequencing (MeDIP-seq) in NSCs (n = 3) and reprogrammed adults NSCs (iPSCs) (n = 3) to compare the methylation profiles, with particular attention to imprinted genes.