Chemoproteomic and Transcriptomic Analysis Reveals that O-GlcNAc Regulates Mouse Embryonic Stem Cell Fate through the Pluripotency Network
© 2023 Wiley-VCH GmbH..
Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. Herein, we report the identification of 979 O-GlcNAcylated proteins and 1340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. Transcriptomic profiling reveals 2456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to mESC fate determination.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Angewandte Chemie (International ed. in English) - 62(2023), 17 vom: 17. Apr., Seite e202300500 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hao, Yi [VerfasserIn] |
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| Links: |
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| Themen: |
Acetylglucosamine |
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| Anmerkungen: |
Date Completed 07.04.2023 Date Revised 17.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/anie.202300500 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a © 2023 Wiley-VCH GmbH. | ||
| 520 | |a Self-renewal and differentiation of embryonic stem cells (ESCs) are influenced by protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification, but the underlying mechanism remains incompletely understood. Herein, we report the identification of 979 O-GlcNAcylated proteins and 1340 modification sites in mouse ESCs (mESCs) by using a chemoproteomics method. In addition to OCT4 and SOX2, the third core pluripotency transcription factor (PTF) NANOG was found to be modified and functionally regulated by O-GlcNAc. Upon differentiation along the neuronal lineage, the O-GlcNAc stoichiometry at 123 sites of 83 proteins-several of which were PTFs-was found to decline. Transcriptomic profiling reveals 2456 differentially expressed genes responsive to OGT inhibition during differentiation, of which 901 are target genes of core PTFs. By acting on the core PTF network, suppression of O-GlcNAcylation upregulates neuron-related genes, thus contributing to mESC fate determination | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chemoproteomics | |
| 650 | 4 | |a Embryonic Stem Cells | |
| 650 | 4 | |a O-Linked β-N-Acetylglucosamine | |
| 650 | 4 | |a Pluripotency Transcription Factors | |
| 650 | 4 | |a Transcriptomics | |
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| 700 | 1 | |a Qin, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yujie |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yanwen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Che |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Guangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Shuyu |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xing |e verfasserin |4 aut | |
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