Neuroectoderm phenotypes in a human stem cell model of O-GlcNAc transferase associated with intellectual disability.
Mol Genet Metab
; 142(2): 108492, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38759397
ABSTRACT
Pathogenic variants in the O-GlcNAc transferase gene (OGT) have been associated with a congenital disorder of glycosylation (OGT-CDG), presenting with intellectual disability which may be of neuroectodermal origin. To test the hypothesis that pathology is linked to defects in differentiation during early embryogenesis, we developed an OGT-CDG induced pluripotent stem cell line together with isogenic control generated by CRISPR/Cas9 gene-editing. Although the OGT-CDG variant leads to a significant decrease in OGT and O-GlcNAcase protein levels, there were no changes in differentiation potential or stemness. However, differentiation into ectoderm resulted in significant differences in O-GlcNAc homeostasis. Further differentiation to neuronal stem cells revealed differences in morphology between patient and control lines, accompanied by disruption of the O-GlcNAc pathway. This suggests a critical role for O-GlcNAcylation in early neuroectoderm architecture, with robust compensatory mechanisms in the earliest stages of stem cell differentiation.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fenotipo
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Diferenciación Celular
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N-Acetilglucosaminiltransferasas
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Placa Neural
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Células Madre Pluripotentes Inducidas
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Discapacidad Intelectual
Límite:
Humans
Idioma:
En
Revista:
Mol Genet Metab
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido