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Reprogramming to recover youthful epigenetic information and restore vision
Yuancheng Lu 1, Benedikt Brommer # 2 3, Xiao Tian # 1, Anitha Krishnan # 3 4, Margarita Meer # 5 6, Chen Wang 2 3, Daniel L Vera 1, Qiurui Zeng 1, Doudou Yu 1, Michael S Bonkowski 1, Jae-Hyun Yang 1, Songlin Zhou 2 3, Emma M Hoffmann 3 4, Margarete M Karg 3 4, Michael B Schultz 1, Alice E Kane 1, Noah Davidsohn 7, Ekaterina Korobkina 3 4, Karolina Chwalek 1, Luis A Rajman 1, George M Church 7, Konrad Hochedlinger 8, Vadim N Gladyshev 5, Steve Horvath 9, Morgan E Levine 6, Meredith S Gregory-Ksander 3 4, Bruce R Ksander 3 4, Zhigang He 2 3, David A Sinclair 10 11
Abstract:
...Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. 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.
PMID: 33268865
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752134/
