小柯机器人

细胞重编程恢复年轻的表观遗传学信息并改善视力
2020-12-03 16:59

美国哈佛医学院David A. Sinclair研究组发现,细胞重新编程可恢复年轻的表观遗传信息并改善视力。相关论文于2020年12月2日在线发表在《自然》杂志上。

使用眼睛作为中枢神经系统组织模型,研究人员发现,小鼠视网膜神经节细胞中Oct4(也称为Pou5f1)、Sox2和Klf4基因(OSK)的异位表达可恢复年轻的DNA甲基化模式和转录组,促进损伤后轴突再生,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需要DNA去甲基化酶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记录(部分通过DNA甲基化编码),可以用来改善组织功能并促进体内再生。

据介绍,衰老是导致组织功能障碍和死亡的退化过程。一种引起衰老的原因是表观遗传噪声的积累破坏了基因的表达方式,导致组织功能和再生能力的下降。随着时间的流逝,DNA甲基化模式的变化构成了衰老时钟的基础,但尚不清楚老年人是否保留恢复这些模式所需的信息,如果可以的话,是否可以改善组织功能。随着时间的流逝,中枢神经系统会失去功能和再生能力。

附:英文原文

Title: Reprogramming to recover youthful epigenetic information and restore vision

Author: Yuancheng Lu, Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, Daniel L. Vera, Qiurui Zeng, Doudou Yu, Michael S. Bonkowski, Jae-Hyun Yang, Songlin Zhou, Emma M. Hoffmann, Margarete M. Karg, Michael B. Schultz, Alice E. Kane, Noah Davidsohn, Ekaterina Korobkina, Karolina Chwalek, Luis A. Rajman, George M. Church, Konrad Hochedlinger, Vadim N. Gladyshev, Steve Horvath, Morgan E. Levine, Meredith S. Gregory-Ksander, Bruce R. Ksander, Zhigang He, David A. Sinclair

Issue&Volume: 2020-12-02

Abstract: 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 capacity1,2,3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, 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 capacity5,6,7. 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.

DOI: 10.1038/s41586-020-2975-4

Source: https://www.nature.com/articles/s41586-020-2975-4

 

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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