O-GlcNAcase regulates pluripotency states of human embryonic stem cells.
Stem Cell Reports
; 19(7): 993-1009, 2024 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-38942028
ABSTRACT
Understanding the regulation of human embryonic stem cells (hESCs) pluripotency is critical to advance the field of developmental biology and regenerative medicine. Despite the recent progress, molecular events regulating hESC pluripotency, especially the transition between naive and primed states, still remain unclear. Here we show that naive hESCs display lower levels of O-linked N-acetylglucosamine (O-GlcNAcylation) than primed hESCs. O-GlcNAcase (OGA), the key enzyme catalyzing the removal of O-GlcNAc from proteins, is highly expressed in naive hESCs and is important for naive pluripotency. Depletion of OGA accelerates naive-to-primed pluripotency transition. OGA is transcriptionally regulated by EP300 and acts as a transcription regulator of genes important for maintaining naive pluripotency. Moreover, we profile protein O-GlcNAcylation of the two pluripotency states by quantitative proteomics. Together, this study identifies OGA as an important factor of naive pluripotency in hESCs and suggests that O-GlcNAcylation has a broad effect on hESCs homeostasis.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Embrionárias Humanas
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article