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Dynamic deformylation of 5-formylcytosine and decarboxylation of 5-carboxylcytosine during differentiation of mouse embryonic stem cells into mouse neurons

文献类型: 外文期刊

作者: Feng, Yang 1 ; Tian, Yang-Qing 3 ; Zhao, Yong-Qiang 1 ; Chen, Sheng-Jun 1 ; Yuan, Bi-Feng 2 ;

作者机构: 1.Chinese Acad Fishery Sci, South China Sea Fisheries Res Inst, Natl R&D Ctr Aquat Prod Proc, Key Lab Aquat Prod Proc,Minist Agr & Rural Affairs, Guangzhou 510300, Peoples R China

2.Wuhan Univ, Renmin Hosp, Res Ctr Publ Hlth, Sch Publ Hlth,Dept Occupat & Environm Hlth, Wuhan 430071, Peoples R China

3.Yunnan Agr Univ, Coll Vet Med, Kunming 650000, Peoples R China

关键词: Metabolic labeling; Mass spectrometry; DNA demethylation; Deformylation; Decarboxylation; C-C cleavage; Mouse embryonic stem cells; Differentiation

期刊名称:CHINESE CHEMICAL LETTERS ( 影响因子:9.4; 五年影响因子:7.3 )

ISSN: 1001-8417

年卷期: 2024 年 35 卷 11 期

页码:

收录情况: SCI

摘要: Regulation of cell fate requires the establishment and erasure of 5-methylcytosine (5mC) in genomic DNA. The formation of 5mC is achieved by DNA cytosine methyltransferases (DNMTs), whereas the removal of 5mC can be accomplished by various pathways. Aside from ten-eleven translocation (TET)-mediated oxidation of 5mC followed by thymine DNA glycosylase (TDG)-initiated base excision repair (BER), the direct deformylation of 5-formylcytosine (5fC) and decarboxylation of 5-carboxylcytosine (5caC) have also been discovered as the novel DNA demethylation pathways. Although these novel demethylation pathways have been identified in stem cells and somatic cells, their precise roles in regulating cell fate remain unclear. Here, we differentiate mouse embryonic stem cells (mESCs) into mouse embryoid bodies (mEBs), followed by further differentiation into mouse neural stem cells (mNSCs) and finally into mouse neurons (mNeurons). During this sequential differentiation process, we employ probe molecules, namely 2' '-fluorinated 5-formylcytidine (F-5fC) and 2' '-fluorinated 5-carboxyldeoxycytidine (F-5caC), for metabolic labeling. The results of mass spectrometry (MS) analysis demonstrate the deformylation and decarboxylation activities are progressively decreased and increased respectively during differentiation process, and this opposite demethylation tendency is not associated with DNMTs and TETs. (c) 2024 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

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