The role of METTL3 in transposable elements regulation and 2C-like program induction in mouse embryonic stem cell

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<sup>6</sup>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<sup>6</sup>A modifications in regulating the transcriptional and developmental plasticity of mESCs and suggest a link between m<sup>6</sup>A loss and the acquisition of a 2C-like state with features of extended potency.

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Publication Details

Journal
Cell Regeneration
Published
2025-11-20
DOI
https://doi.org/10.1186/s13619-025-00262-w
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

The role of METTL3 in transposable elements regulation and 2C-like program induction in mouse embryonic stem cell

Xiongzhi Quan, Mingqiang Deng, Yingying Zhao, Jiekai Chen et al.
Cell Regeneration
RNA modifications and cancer
article

The role of METTL3 in transposable elements regulation and 2C-like program induction in mouse embryonic stem cell

Xiongzhi Quan, Mingqiang Deng, Yingying Zhao, Jiekai Chen, Kaixin Wu, Xiuyu Chen, Bingqiu Chen, Lingmei Jin, Xichen Bao, Jie Wang, Danfeng Li, Zongyao Wen, Jia‐Jie Hao
article en

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<sup>6</sup>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<sup>6</sup>A modifications in regulating the transcriptional and developmental plasticity of mESCs and suggest a link between m<sup>6</sup>A loss and the acquisition of a 2C-like state with features of extended potency.

Cell RegenerationVol. 14(1)
Department of Health (CN), Guangzhou Institutes of Biomedicine and Health (CN), Guangzhou University (CN), University of Chinese Academy of Sciences (CN), University of Hong Kong (HK), Guangzhou Medical University (CN)
National Natural Science Foundation of China, Sun Yat-sen University, 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 Percentile: Top 69%
RNA modifications and cancer
DOIOpen Access PDFOpenAlex
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