| Lnc956 regulates mouse embryonic stem cell differentiation in response to DNA damage in a p53-independent pathway |
| Ma, HX; Ning, YQ; Wang, L; Zhang, WD; Zheng, P
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| 2023
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| 发表期刊 | SCIENCE ADVANCES
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| ISSN | 2375-2548
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| 卷号 | 9期号:3 |
| 摘要 | Maintaining genomic stability is crucial for embryonic stem cells (ESCs). ESCs with unrepaired DNA damage are eliminated through differentiation and apoptosis. To date, only tumor suppressor p53 is known to be implicated in this quality control process. Here, we identified a p53-independent quality control factor lncRNA NONMMUT028956 (Lnc956 for short) in mouse ESCs. Lnc956 is prevalently expressed in ESCs and regulates the differentiation of ESCs after DNA damage. Mechanistically, Ataxia telangiectasia mutated (ATM) activation drives m6A methylation of Lnc956, which promotes its interaction with Kruppel-like factor 4 (KLF4). Lnc956-KLF4 association sequestrates the KLF4 protein and prevents KLF4's transcriptional regulation on pluripotency. This posttranslational mechanism favors the rapid shutdown of the regulatory circuitry of pluripotency. Thus, ATM signaling in ESCs can activate two pathways mediated by p53 and Lnc956, respectively, which act together to ensure robust differentiation and apoptosis in response to unrepaired DNA damage. |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13983
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| 专题 | 科研部门_哺乳动物胚胎发育（郑萍）
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推荐引用方式
GB/T 7714 |
Ma, HX,Ning, YQ,Wang, L,et al. Lnc956 regulates mouse embryonic stem cell differentiation in response to DNA damage in a p53-independent pathway[J]. SCIENCE ADVANCES,2023,9(3).
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| APA |
Ma, HX,Ning, YQ,Wang, L,Zhang, WD,&Zheng, P.(2023).Lnc956 regulates mouse embryonic stem cell differentiation in response to DNA damage in a p53-independent pathway.SCIENCE ADVANCES,9(3).
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| MLA |
Ma, HX,et al."Lnc956 regulates mouse embryonic stem cell differentiation in response to DNA damage in a p53-independent pathway".SCIENCE ADVANCES 9.3(2023).
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