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An O-GlcNAc transferase pathogenic variant that affects pluripotent stem cell self-renewal

Omelkova, M.; Fenger, C. D.; Murray, M.; Hammer, T. B.; Pravata, V. M.; Bartual, S.; Czajewski, I.; Bayat, A.; Ferenbach, A. T.; Stavridis, M.; van Aalten, D. M. F.

2023-03-13 molecular biology
10.1101/2023.03.13.531514 bioRxiv
Show abstract

O-linked {beta}-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. Inborn OGT genetic variants were recently shown to mediate a novel type of Congenital Disorder of Glycosylation (OGT-CDG) which is characterized by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Y variant which co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Y show decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4, Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome. Summary statementWe show that the C921Y O-GlcNAc transferase variant found in patients with intellectual disability leads to a defect in pluripotent stem cell self-renewal and decreased levels of stem cell markers.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.