Global Profiling of the Lysine Crotonylome in Different Pluripotent States
| Autor: | Yuan Lv, Jin Meng, Chen Bu, Giacomo Volpe, Zhongyi Cheng, Jiekai Chen, Carl Ward, Jieyi Hu, Lin Guo, Miguel A. Esteban, Mengling Jiang, Xichen Bao |
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| Rok vydání: | 2021 |
| Předmět: |
Pluripotency
Proteome RNA-binding proteins RNA-binding protein Crotonylation Cell fate determination Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry Gene expression Genetics Animals Induced pluripotent stem cell Molecular Biology Original Research 030304 developmental biology 0303 health sciences Proteasome Chemistry Lysine Cell biology Computational Mathematics Metabolism Protein Processing Post-Translational Developmental biology 030217 neurology & neurosurgery Function (biology) Biogenesis Chromatography Liquid |
| Zdroj: | Genomics, Proteomics & Bioinformatics |
| ISSN: | 1672-0229 |
| DOI: | 10.1016/j.gpb.2021.01.004 |
| Popis: | Pluripotent stem cells (PSCs) can be expanded in vitro in different culture conditions, resulting in a spectrum of cell states with distinct properties. Understanding how PSCs transition from one state to another, ultimately leading to lineage-specific differentiation, is important for developmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifications of proteins. Protein crotonylation is a newly discovered post-translational modification where lysine residues are modified with a crotonyl group. Here, we employed affinity purification of crotonylated peptides and liquid chromatography–tandem mass spectrometry (LC–MS/MS) to systematically profile protein crotonylation in mouse PSCs in different states including ground, metastable, and primed states, as well as metastable PSCs undergoing early pluripotency exit. We successfully identified 3628 high-confidence crotonylated sites in 1426 proteins. These crotonylated proteins are enriched for factors involved in functions/processes related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasome function. Moreover, we found that increasing the cellular levels of crotonyl-coenzyme A (crotonyl-CoA) through crotonic acid treatment promotes proteasome activity in metastable PSCs and delays their differentiation, consistent with previous observations showing that enhanced proteasome activity helps to sustain pluripotency. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of metabolism in other cell fate transitions. |
| Databáze: | OpenAIRE |
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