The role of METTL3 in transposable elements regulation and 2C-like program induction in mouse embryonic stem cell
Year: 2025
Type: article
Abstract: METTL3 is a crucial mRNA methyltransferase in mammals, essential for the regulation of gene expression and various biological processes. Here, we demonstrate that Mettl3 knockout (KO) in mouse embryonic stem cells (mESCs) leads to widespread upregulation of transposable elements (TEs) and 2-cell (2C)-like genes in a m 6 A enzyme activity-dependent manner, independent of culture conditions. Furthermore, embryo chimera experiments using a transient METTL3 degradation system (dTAG) revealed that METTL3-deficient mESCs can contribute to trophectoderm lineages at the blastocyst stage, indicative of expanded developmental potential. These findings highlight the role of METTL3-mediated m 6 A modifications in regulating the transcriptional and developmental plasticity of mESCs and suggest a link between m 6 A loss and the acquisition of a 2C-like state with features of extended potency.
Source: Cell Regeneration
Authors: Xiuyu Chen, Bingqiu Chen, Yingying Zhao, Ziyi Wen, Jiajie Hao, Lingmei Jin, Danfeng Li, Xiongzhi Quan, Kaixin Wu, Mingqiang Deng, Xichen Bao, Jie Wang, Jiekai Chen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: National Natural Science Foundation of China, Sun Yat-sen University, Key Technologies Research and Development Program, National Key Research and Development Program of China, Science and Technology Planning Project of Guangdong Province, Basic and Applied Basic Research Foundation of Guangdong Province
OpenAlex ID: W4416398307