Reprogramming to recover youthful epigenetic information and restore vision.
Reprogramming to recover youthful epigenetic information and restore vision.
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DOI：
10.1038/s41586-020-2975-4
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发表时间：
2020-12
期刊：
影响因子：
64.8
通讯作者：
Sinclair DA
中科院分区：
文献类型：
--
作者：
Lu Y;Brommer B;Tian X;Krishnan A;Meer M;Wang C;Vera DL;Zeng Q;Yu D;Bonkowski MS;Yang JH;Zhou S;Hoffmann EM;Karg MM;Schultz MB;Kane AE;Davidsohn N;Korobkina E;Chwalek K;Rajman LA;Church GM;Hochedlinger K;Gladyshev VN;Horvath S;Levine ME;Gregory-Ksander MS;Ksander BR;He Z;Sinclair DA
衰老是一个退化的过程，会导致组织功能障碍和死亡。衰老的一个原因被认为是表观遗传噪音的积累，它扰乱了基因表达模式，导致组织功能和再生能力下降。随着时间的推移，DNA甲基化模式的变化构成了衰老时钟的基础，但老年人是否保留了恢复这些模式所需的信息--如果是的话，这是否可以改善组织功能--尚不清楚。随着时间的推移，中枢神经系统(CNS)会失去功能和再生能力。以眼为模型中枢神经系统组织，我们发现在小鼠视网膜神经节细胞中异位表达Oct4(也称为Pou5f1)、Sox2和Klf4基因(OSK)可以恢复年轻的DNA甲基化模式和转录本，促进损伤后轴突的再生，并逆转青光眼小鼠模型和老年小鼠的视力丧失。OSK诱导的轴突再生和视觉重编程的有益效果需要DNA去甲基酶TET1和TET2。这些数据表明，哺乳动物组织保留了年轻的表观遗传信息的记录-部分由DNA甲基化编码-可以访问这些信息以改善组织功能并促进体内再生。
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to DNA methylation patterns over time form the basis of ageing clocks, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
64.8
作者：
Abad, Maria;Mosteiro, Lluc;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group
DOI：
10.18632/aging.100742
发表时间：
2015-05
期刊：
Aging
影响因子：
--
作者：
Horvath S;Mah V;Lu AT;Woo JS;Choi OW;Jasinska AJ;Riancho JA;Tung S;Coles NS;Braun J;Vinters HV;Coles LS
通讯作者：
Coles LS