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J Proteome Res. 2018 Jul 6;17(7):2491-2498. doi: 10.1021/acs.jproteome.8b00238. Epub 2018 Jun 21.

Quantitative Dynamics of Proteome, Acetylome, and Succinylome during Stem-Cell Differentiation into Hepatocyte-like Cells.

Author information

1
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China , Collaborative Innovation Center for Cancer Medicine , Guangzhou 510060 , China.
2
Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease , Stomatology Hospital of Guangzhou Medical University , Guangzhou 510140 , China.
3
Jingjie PTM BioLabs (Hangzhou), Co. Ltd. , Hangzhou 310018 , China.
4
Department of Thoracic Surgery , China Meitan General Hospital , Beijing 100028 , China.
5
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology , Tongji University , Shanghai 200092 , China.

Abstract

Stem-cell differentiation is a complex biological process controlled by a series of functional protein clusters and signaling transductions, especially metabolism-related pathways. Although previous studies have quantified the proteome and phosphoproteome for stem-cell differentiation, the investigation of acylation-mediated regulation is still absent. In this study, we quantitatively profiled the proteome, acetylome, and succinylome in pluripotent human embryonic stem cells (hESCs) and differentiated hepatocyte-like cells (HLCs). In total, 3843 proteins, 185 acetylation sites in 103 proteins, and 602 succinylation sites in 391 proteins were quantified. The quantitative proteome showed that in differentiated HLCs the TGF-β, JAK-STAT, and RAS signaling pathways were activated, whereas ECM-related processes such as sulfates and leucine degradation were depressed. Interestingly, it was observed that the acetylation and succinylation were more intensive in hESCs, whereas protein processing in endoplasmic reticulum and the carbon metabolic pathways were especially highly succinylated. Because the metabolism patterns in pluripotent hESCs and the differentiated HLCs were different, we proposed that the dynamic acylations, especially succinylation, might regulate the Warburg-like effect and TCA cycle during differentiation. Taken together, we systematically profiled the protein and acylation levels of regulation in pluripotent hESCs and differentiated HLCs, and the results indicated the important roles of acylation in pluripotency maintenance and differentiation.

KEYWORDS:

acetylation; differentiation; metabolism; proteome; stem cell; succinylation

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