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

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

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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 ox-idation of 5mC followed by thymine DNA glycosylase(TDG)-initiated base excision repair(BER),the di-rect 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 path-ways have been identified in stem cells and somatic cells,their precise roles in regulating cell fate re-main 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 decarboxy-lation activities are progressively decreased and increased respectively during differentiation process,and this opposite demethylation tendency is not associated with DNMTs and TETs.

Metabolic labelingMass spectrometryDNA demethylationDeformylationDecarboxylationC-C cleavageMouse embryonic stem cellsDifferentiation

Yang Feng、Yang-Qing Tian、Yong-Qiang Zhao、Sheng-Jun Chen、Bi-Feng Yuan

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Key Laboratory of Aquatic Product Processing,Ministry of Agriculture and Rural Affairs,National R&D Center for Aquatic Product Processing,South China Sea Fisheries Research Institute,Chinese Academy of Fishery Sciences,Guangzhou 510300,China

Department of Occupational and Environmental Health,School of Public Health,Research Center of Public Health,Renmin Hospital of Wuhan University,Wuhan University,Wuhan 430071,China

College of Veterinary Medicine,Yunnan Agricultural University,Kunming 650000,China

2024

10.1016/j.cclet.2024.109656

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(11)