| Summary: | Summary: The parent-specific monoallelic expression of imprinted genes is controlled by DNA methylation marks that are established differentially in the germline. Perturbation of these marks leads to loss of imprinting (LOI), which is associated with developmental disorders and malignancy and may also obstruct applications of human pluripotent stem cells (hPSCs). Previous studies of LOI in hPSCs were performed on relatively small numbers of cell lines, often leading to conflicting conclusions regarding imprinting stability. Here, we chart the landscape of LOI in hPSCs by applying a large-scale analysis of allele-specific RNA-seq data from more than 270 hPSC samples. We show that reprogrammed hPSCs acquire higher levels of LOI compared with embryonic stem cells and that LOI can pre-exist in their somatic cells of origin. Furthermore, different imprinted genes vary with respect to LOI incidence, surprisingly revealing that those controlled paternally are more prone to disruption. Our findings emphasize the importance of inspecting the imprinting status of hPSCs. : Bar et al. present a large-scale analysis of loss of imprinting (LOI) in human pluripotent stem cells (hPSCs). They demonstrate differences in LOI abundance between hPSCs depending on their derivation method and between imprinted genes according to their parent of origin. This should be considered in future applications of hPSCs. Keywords: pluripotent stem cells, embryonic stem cells, parental imprinting, maternal genes, paternal genes, DNA methylation, monoallelic expression
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