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

Standard

An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. / Omelková, Michaela; Fenger, Christina Dühring; Murray, Marta; Hammer, Trine Bjørg; Pravata, Veronica M.; Bartual, Sergio Galan; Czajewski, Ignacy; Bayat, Allan; Ferenbach, Andrew T.; Stavridis, Marios P.; van Aalten, Daan M.F.

In: DMM Disease Models and Mechanisms, Vol. 16, No. 6, dmm049132, 06.2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Omelková, M, Fenger, CD, Murray, M, Hammer, TB, Pravata, VM, Bartual, SG, Czajewski, I, Bayat, A, Ferenbach, AT, Stavridis, MP & van Aalten, DMF 2023, 'An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal', DMM Disease Models and Mechanisms, vol. 16, no. 6, dmm049132. https://doi.org/10.1242/dmm.049132

APA

Omelková, M., Fenger, C. D., Murray, M., Hammer, T. B., Pravata, V. M., Bartual, S. G., Czajewski, I., Bayat, A., Ferenbach, A. T., Stavridis, M. P., & van Aalten, D. M. F. (2023). An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. DMM Disease Models and Mechanisms, 16(6), [dmm049132]. https://doi.org/10.1242/dmm.049132

Vancouver

Omelková M, Fenger CD, Murray M, Hammer TB, Pravata VM, Bartual SG et al. An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. DMM Disease Models and Mechanisms. 2023 Jun;16(6). dmm049132. https://doi.org/10.1242/dmm.049132

Author

Omelková, Michaela ; Fenger, Christina Dühring ; Murray, Marta ; Hammer, Trine Bjørg ; Pravata, Veronica M. ; Bartual, Sergio Galan ; Czajewski, Ignacy ; Bayat, Allan ; Ferenbach, Andrew T. ; Stavridis, Marios P. ; van Aalten, Daan M.F. / An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal. In: DMM Disease Models and Mechanisms. 2023 ; Vol. 16, No. 6.

Bibtex

@article{ff91651303f042bfa7fc0f503a8a240b,
title = "An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal",
abstract = "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. ",
keywords = "Congenital disorders of glycosylation, Intellectual disability, O-GlcNAc, OGT, Self-renewal, Stem cells",
author = "Michaela Omelkov{\'a} and Fenger, {Christina D{\"u}hring} and Marta Murray and Hammer, {Trine Bj{\o}rg} and Pravata, {Veronica M.} and Bartual, {Sergio Galan} and Ignacy Czajewski and Allan Bayat and Ferenbach, {Andrew T.} and Stavridis, {Marios P.} and {van Aalten}, {Daan M.F.}",
note = "Publisher Copyright: {\textcopyright} 2023. Published by The Company of Biologists Ltd.",
year = "2023",
month = jun,
doi = "10.1242/dmm.049132",
language = "English",
volume = "16",
journal = "Disease Models & Mechanisms",
issn = "1754-8403",
publisher = "company of biologists",
number = "6",

}

RIS

TY - JOUR

T1 - An O-GlcNAc transferase pathogenic variant linked to intellectual disability affects pluripotent stem cell self-renewal

AU - Omelková, Michaela

AU - Fenger, Christina Dühring

AU - Murray, Marta

AU - Hammer, Trine Bjørg

AU - Pravata, Veronica M.

AU - Bartual, Sergio Galan

AU - Czajewski, Ignacy

AU - Bayat, Allan

AU - Ferenbach, Andrew T.

AU - Stavridis, Marios P.

AU - van Aalten, Daan M.F.

N1 - Publisher Copyright: © 2023. Published by The Company of Biologists Ltd.

PY - 2023/6

Y1 - 2023/6

N2 - 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.

AB - 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.

KW - Congenital disorders of glycosylation

KW - Intellectual disability

KW - O-GlcNAc

KW - OGT

KW - Self-renewal

KW - Stem cells

U2 - 10.1242/dmm.049132

DO - 10.1242/dmm.049132

M3 - Journal article

C2 - 37334838

AN - SCOPUS:85162652512

VL - 16

JO - Disease Models & Mechanisms

JF - Disease Models & Mechanisms

SN - 1754-8403

IS - 6

M1 - dmm049132

ER -

ID: 389676542