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Reprogramming to recover youthful epigenetic information and restore vision

Nature (London), 2020-12, Vol.588 (7836), p.124-129 [Peer Reviewed Journal]

Copyright Nature Publishing Group Dec 3, 2020 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-020-2975-4 ;PMID: 33268865

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Title:
Reprogramming to recover youthful epigenetic information and restore vision
Author: Lu, Yuancheng ; Brommer, Benedikt ; Tian, Xiao ; Krishnan, Anitha ; Meer, Margarita ; Wang, Chen ; Vera, Daniel L ; Zeng, Qiurui ; Yu, Doudou ; Bonkowski, Michael S ; Yang, Jae-Hyun ; Zhou, Songlin ; Hoffmann, Emma M ; Karg, Margarete M ; Schultz, Michael B ; Kane, Alice E ; Davidsohn, Noah ; Korobkina, Ekaterina ; Chwalek, Karolina ; Rajman, Luis A ; Church, George M ; Hochedlinger, Konrad ; Gladyshev, Vadim N ; Horvath, Steve ; Levine, Morgan E ; Gregory-Ksander, Meredith S ; Ksander, Bruce R ; He, Zhigang ; Sinclair, David A
Subjects: Aging ; Aging - genetics ; Aging - physiology ; Animals ; Axons - physiology ; Cell Line, Tumor ; Cell Survival ; Cellular Reprogramming - genetics ; Central nervous system ; Deoxyribonucleic acid ; Dependovirus - genetics ; Dioxygenases ; Disease Models, Animal ; DNA ; DNA Methylation ; DNA-Binding Proteins - genetics ; Ectopic expression ; Epigenesis, Genetic ; Epigenetics ; Eye - cytology ; Eye - innervation ; Eye - pathology ; Female ; Gene expression ; Genetic Vectors - genetics ; Glaucoma ; Glaucoma - genetics ; Glaucoma - pathology ; Humans ; KLF4 protein ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors - genetics ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration - genetics ; Oct-4 protein ; Octamer Transcription Factor-3 - genetics ; Optic Nerve Injuries - genetics ; Proto-Oncogene Proteins - genetics ; Regeneration ; Retinal ganglion cells ; Retinal Ganglion Cells - cytology ; SOXB1 Transcription Factors - genetics ; Tissues ; Transcriptome - genetics ; Vision ; Vision, Ocular - genetics ; Vision, Ocular - physiology
Is Part Of: Nature (London), 2020-12, Vol.588 (7836), p.124-129
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/s41586-020-2975-4
PMID: 33268865
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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Reprogramming to recover youthful epigenetic information and restore vision

Copyright Nature Publishing Group Dec 3, 2020 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-020-2975-4 ;PMID: 33268865

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