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Tet1 调节成年海马神经发生和认知。

Tet1 regulates adult hippocampal neurogenesis and cognition.

机构信息

The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Cell Stem Cell. 2013 Aug 1;13(2):237-45. doi: 10.1016/j.stem.2013.05.006. Epub 2013 Jun 13.

DOI:10.1016/j.stem.2013.05.006
PMID:23770080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4474382/
Abstract

DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in embryonic stem cells and neurons in mammals. However, its biological function in vivo is largely unknown. Here, we demonstrate that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain. Mice lacking Tet1 exhibit impaired hippocampal neurogenesis accompanied by poor learning and memory. In adult neural progenitor cells deficient in Tet1, a cohort of genes involved in progenitor proliferation were hypermethylated and downregulated. Our results indicate that Tet1 is positively involved in the epigenetic regulation of neural progenitor cell proliferation in the adult brain.

摘要

Tet 双加氧酶催化的 DNA 羟化在哺乳动物的胚胎干细胞和神经元中大量发生。然而,其在体内的生物学功能在很大程度上仍是未知的。在这里,我们证明 Tet1 在调节成年小鼠大脑中的神经祖细胞增殖方面起着重要作用。缺乏 Tet1 的小鼠表现出海马神经发生受损,伴有学习和记忆能力差。在缺乏 Tet1 的成年神经祖细胞中,一组参与祖细胞增殖的基因被超甲基化和下调。我们的结果表明,Tet1 积极参与成年大脑中神经祖细胞增殖的表观遗传调控。

相似文献

1
Tet1 regulates adult hippocampal neurogenesis and cognition.Tet1 调节成年海马神经发生和认知。
Cell Stem Cell. 2013 Aug 1;13(2):237-45. doi: 10.1016/j.stem.2013.05.006. Epub 2013 Jun 13.
2
On your (methyl) mark, get TET1, go!启动(甲基)化,获取 TET1,开始!
Cell Stem Cell. 2013 Aug 1;13(2):133-4. doi: 10.1016/j.stem.2013.07.011.
3
Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring.胎儿生长受限通过 Tet1 损害后代海马神经发生和认知功能。
Cell Rep. 2021 Nov 2;37(5):109912. doi: 10.1016/j.celrep.2021.109912.
4
Ten-Eleven Translocation 1 and 2 Confer Overlapping Transcriptional Programs for the Proliferation of Cultured Adult Neural Stem Cells.10-11易位蛋白1和2为培养的成体神经干细胞增殖赋予重叠的转录程序。
Cell Mol Neurobiol. 2017 Aug;37(6):995-1008. doi: 10.1007/s10571-016-0432-6. Epub 2016 Oct 24.
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Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories the activation of calcium-dependent cascade through Egr1 expression in mice.Tet1 过表达导致小鼠出现类似焦虑的行为和增强的恐惧记忆,这是通过 Egr1 表达激活钙依赖性级联反应所致。
FASEB J. 2018 Jan;32(1):390-403. doi: 10.1096/fj.201601340RR. Epub 2017 Sep 12.
6
Tis21 expression marks not only populations of neurogenic precursor cells but also new postmitotic neurons in adult hippocampal neurogenesis.Tis21 的表达不仅标志着神经前体细胞群体,也标志着成年海马神经发生中的新有丝分裂后神经元。
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7
DSCR1-mediated TET1 splicing regulates miR-124 expression to control adult hippocampal neurogenesis.DSCR1 介导的 TET1 剪接调控 miR-124 的表达,从而控制成年海马神经发生。
EMBO J. 2019 Jul 15;38(14):e101293. doi: 10.15252/embj.2018101293. Epub 2019 Jun 11.
8
Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis.PTEN 缺失导致成年海马神经干细胞/祖细胞的细胞异常,并改变神经发生。
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Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model.核受体 TLX 刺激海马神经发生,并增强转基因小鼠模型的学习和记忆。
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9115-20. doi: 10.1073/pnas.1406779111. Epub 2014 Jun 10.
10
TET1 Deficiency Impairs Morphogen-free Differentiation of Human Embryonic Stem Cells to Neuroectoderm.TET1 缺失可损害人胚胎干细胞在无形态发生素条件下向神经外胚层的分化。
Sci Rep. 2020 Jun 25;10(1):10343. doi: 10.1038/s41598-020-67143-x.

引用本文的文献

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TET1: The epigenetic architect of clinical disease progression.TET1:临床疾病进展的表观遗传构建者。
Genes Dis. 2025 Jan 4;12(5):101513. doi: 10.1016/j.gendis.2025.101513. eCollection 2025 Sep.
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Maternal Vitamin C Deficiency and Genetic Risk Factors Contribute to Congenital Defects through Dysregulation of DNA Methylation.母体维生素C缺乏和遗传风险因素通过DNA甲基化失调导致先天性缺陷。
bioRxiv. 2025 May 30:2025.05.27.656260. doi: 10.1101/2025.05.27.656260.
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Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.临床前研究中缺血性中风的潜在治疗靶点:表观遗传修饰酶DNMT/TET和HAT/HDAC。
Front Pharmacol. 2025 Apr 28;16:1571276. doi: 10.3389/fphar.2025.1571276. eCollection 2025.
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DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis.DNA羟甲基化酶Tet1和Tet2通过IGF-1/mTOR信号轴调节骨骼衰老和骨髓基质细胞代谢。
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How do neurons live long and healthy? The mechanism of neuronal genome integrity.神经元如何实现长期健康存活?神经元基因组完整性的机制。
Front Neurosci. 2025 Mar 19;19:1552790. doi: 10.3389/fnins.2025.1552790. eCollection 2025.
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Liver TET1 promotes metabolic dysfunction-associated steatotic liver disease.肝脏TET1促进代谢功能障碍相关的脂肪性肝病。
EMBO Mol Med. 2025 May;17(5):1101-1117. doi: 10.1038/s44321-025-00224-4. Epub 2025 Mar 31.
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TET1 mitigates prenatal fluoride-induced cognition impairment by modulating Bcl2 DNA hydroxymethylation level.TET1通过调节Bcl2 DNA羟甲基化水平减轻产前氟诱导的认知障碍。
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DNA Methylation in Long-Term Memory.长期记忆中的DNA甲基化
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Hippocampal gene expression changes associated with sequential behavioral training in a temporal lobe epilepsy rat model.颞叶癫痫大鼠模型中与序贯行为训练相关的海马基因表达变化
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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.探索2-酮戊二酸依赖性双加氧酶的抗坏血酸需求
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本文引用的文献

1
Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis.哺乳动物神经发生中 5-羟甲基胞嘧啶和染色质标记的动态变化。
Cell Rep. 2013 Feb 21;3(2):291-300. doi: 10.1016/j.celrep.2013.01.011. Epub 2013 Feb 9.
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Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development.Tet1 和 Tet2 联合缺失导致表观遗传异常,但与出生后发育相容。
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MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system.MECP2 与神经系统中富含 5hmC 的活跃基因和可及染色质结合。
Cell. 2012 Dec 21;151(7):1417-30. doi: 10.1016/j.cell.2012.11.022.
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Tet1 controls meiosis by regulating meiotic gene expression.Tet1 通过调节减数分裂基因表达来控制减数分裂。
Nature. 2012 Dec 20;492(7429):443-7. doi: 10.1038/nature11709. Epub 2012 Nov 14.
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Base-resolution analysis of 5-hydroxymethylcytosine in the mammalian genome.哺乳动物基因组中 5-羟甲基胞嘧啶的碱基分辨率分析。
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Tet family proteins and 5-hydroxymethylcytosine in development and disease.Tet 家族蛋白与 5-羟甲基胞嘧啶在发育和疾病中的作用。
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Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation.Tet 蛋白介导的 5-甲基胞嘧啶氧化的机制和功能。
Genes Dev. 2011 Dec 1;25(23):2436-52. doi: 10.1101/gad.179184.111.
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Uncovering the role of 5-hydroxymethylcytosine in the epigenome.揭示 5-羟甲基胞嘧啶在表观基因组中的作用。
Nat Rev Genet. 2011 Nov 15;13(1):7-13. doi: 10.1038/nrg3080.
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5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.5-羟甲基胞嘧啶介导的出生后神经发育和衰老过程中的表观遗传动态变化。
Nat Neurosci. 2011 Oct 30;14(12):1607-16. doi: 10.1038/nn.2959.
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Neuronal activity modifies the DNA methylation landscape in the adult brain.神经元活性可改变成年大脑中的 DNA 甲基化图谱。
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