An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal
Research output: Contribution to journal › Journal article › Research › peer-review
O-linked β-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 hdisorder of glycosylation (OGT-CDG), which is characterised by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Y variant that co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Y showed decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4 (encoded by Pou5f1), 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.
Original language | English |
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Article number | dmm049132 |
Journal | DMM Disease Models and Mechanisms |
Volume | 16 |
Issue number | 6 |
ISSN | 1754-8403 |
DOIs | |
Publication status | Published - Jun 2023 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:
© 2023. Published by The Company of Biologists Ltd.
- Congenital disorders of glycosylation, Intellectual disability, O-GlcNAc, OGT, Self-renewal, Stem cells
Research areas
ID: 389676542