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Reprogramming to recover youthful epigenetic information and restore vision.
- Source :
-
Nature [Nature] 2020 Dec; Vol. 588 (7836), pp. 124-129. Date of Electronic Publication: 2020 Dec 02. - Publication Year :
- 2020
-
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 capacity <superscript>1-3</superscript> . Changes to DNA methylation patterns over time form the basis of ageing clocks <superscript>4</superscript> , 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 <superscript>5-7</superscript> . 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.
- Subjects :
- Aging physiology
Animals
Axons physiology
Cell Line, Tumor
Cell Survival
DNA-Binding Proteins genetics
Dependovirus genetics
Dioxygenases
Disease Models, Animal
Female
Genetic Vectors genetics
Glaucoma genetics
Glaucoma pathology
Humans
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors genetics
Mice
Mice, Inbred C57BL
Octamer Transcription Factor-3 genetics
Optic Nerve Injuries genetics
Proto-Oncogene Proteins genetics
Retinal Ganglion Cells cytology
SOXB1 Transcription Factors genetics
Transcriptome genetics
Aging genetics
Cellular Reprogramming genetics
DNA Methylation
Epigenesis, Genetic
Eye cytology
Eye innervation
Eye pathology
Nerve Regeneration genetics
Vision, Ocular genetics
Vision, Ocular physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 588
- Issue :
- 7836
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 33268865
- Full Text :
- https://doi.org/10.1038/s41586-020-2975-4