The Hebrew University of Jerusalem Jerusalem, Israel
Abstract: Genomic imprinting, an epigenetic process resulting in parent-specific gene expression, is essential for normal development and growth. Disruption of imprinting leads to various developmental disorders and cancers, yet our understanding of the full repertoire of imprinted genes in humans remains incomplete. Here, we utilized androgenetic, parthenogenetic, and biparental human embryonic stem cells and their neural derivatives to identify novel imprinted genes by analyzing their methylome and transcriptome profiles. Our analysis revealed 12 novel imprinted genes distributed across four distinct loci, with six of them clustered in an uncharacterized imprinted region on chromosome 19. We identified potential imprinting control regions regulating this novel cluster, suggesting a coordinated regulatory mechanism. Notably, these imprinted genes are enriched in neurodevelopmental functions and cancer-related pathways, with several showing isoform-specific imprinting patterns. Our analysis also revealed consistent DNA methylation aberrations in pluripotent stem cells at specific imprinted loci, highlighting potential epigenetic instability during culturing. These findings significantly expand our understanding of genomic imprinting regulation and its implications in human development and disease.
