Global Profiling of the Lysine Crotonylome in Different Pluripotent States
- Author:
Lv YUAN
1
,
2
,
3
;
Bu CHEN
;
Meng JIN
;
Ward CARL
;
Volpe GIACOMO
;
Hu JIEYI
;
Jiang MENGLING
;
Guo LIN
;
Chen JIEKAI
;
A.Esteban MIGUEL
;
Bao XICHEN
;
Cheng ZHONGYI
Author Information
1. Laboratory of Integrative Biology,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China
2. CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China
3. University of Chinese Academy of Sciences,Beiji
- Keywords:
Metabolism;
Crotonylation;
Pluripotency;
RNA-binding proteins;
Proteasome
- From:
Genomics, Proteomics & Bioinformatics
2021;19(1):80-93
- CountryChina
- Language:Chinese
-
Abstract:
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 devel-opmental biology and regenerative medicine. Although there is significant information regarding gene expression changes controlling these transitions, less is known about post-translational modifi-cations 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 includ-ing 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, consis-tent with previous observations showing that enhanced proteasome activity helps to sustain pluripo-tency. 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.
