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Global Profiling of the Lysine Crotonylome in Different Pluripotent States
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498919/ https://www.ncbi.nlm.nih.gov/pubmed/33746086 http://dx.doi.org/10.1016/j.gpb.2021.01.004 |
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author | Lv, Yuan Bu, Chen Meng, Jin Ward, Carl Volpe, Giacomo Hu, Jieyi Jiang, Mengling Guo, Lin Chen, Jiekai Esteban, Miguel A. Bao, Xichen Cheng, Zhongyi |
author_facet | Lv, Yuan Bu, Chen Meng, Jin Ward, Carl Volpe, Giacomo Hu, Jieyi Jiang, Mengling Guo, Lin Chen, Jiekai Esteban, Miguel A. Bao, Xichen Cheng, Zhongyi |
author_sort | Lv, Yuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8498919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84989192021-10-12 Global Profiling of the Lysine Crotonylome in Different Pluripotent States Lv, Yuan Bu, Chen Meng, Jin Ward, Carl Volpe, Giacomo Hu, Jieyi Jiang, Mengling Guo, Lin Chen, Jiekai Esteban, Miguel A. Bao, Xichen Cheng, Zhongyi Genomics Proteomics Bioinformatics Original Research 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. Elsevier 2021-02 2021-03-19 /pmc/articles/PMC8498919/ /pubmed/33746086 http://dx.doi.org/10.1016/j.gpb.2021.01.004 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Lv, Yuan Bu, Chen Meng, Jin Ward, Carl Volpe, Giacomo Hu, Jieyi Jiang, Mengling Guo, Lin Chen, Jiekai Esteban, Miguel A. Bao, Xichen Cheng, Zhongyi Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title | Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title_full | Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title_fullStr | Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title_full_unstemmed | Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title_short | Global Profiling of the Lysine Crotonylome in Different Pluripotent States |
title_sort | global profiling of the lysine crotonylome in different pluripotent states |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498919/ https://www.ncbi.nlm.nih.gov/pubmed/33746086 http://dx.doi.org/10.1016/j.gpb.2021.01.004 |
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