Apobec1 Promotes Neurotoxicity-Induced Dedifferentiation of Müller Glial Cells.
Retinal Müller glial cells in mammals acquire stem and progenitor cell properties after neurotoxic treatment. However, the molecular mechanisms underlying proliferation and dedifferentiation of adult Müller cells in the mammalian retina were unclear. In this study, treatments with N-methyl-D-aspartate (NMDA) plus epidermal growth factor (EGF) led to the proliferation of Müller cells and expression of stem cell markers including Nanog and Nestin in the retina. The increased mRNA for Nanog and Nestin were coincident with reduced methylation of a Nanog promoter and a Nestin enhancer specific in the neural stem cells, respectively. We found that Apolipoprotein B mRNA editing catalytic subunit 1 (Apobec1) was upregulated early in the retina treated with NMDA and EGF. Moreover, overexpression of Apobec1 in primary Müller cells increased expression of Nestin and reduced methylation of the Nestin enhancer. The data suggest that neurotoxicity-induced Apobec1 may promote expression of Nestin and help cell cycle reentry of retinal Müller cells via DNA demethylation. This study provides novel insights into the molecular mechanisms underlying dedifferentiation and proliferation of Müller cells in the mammalian retina.
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Jian
J
Xiao
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Xue
X
Li
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Lan
L
Chen
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Xin
X
Han
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Wei
W
Zhao
Shengli Oilfield Central Hospital, Dongying, Shandong, 257034, China.
Lianlian
L
Li
School of Ophthalmology and Optometry and Eye Hospital, China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, National Ministry of Health of China, and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China. jgchen@mail.eye.ac.cn.|Key Laboratory of Visual Science, National Ministry of Health, and School of Optometry and Ophthalmology, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, Zhejiang, 325027, People's Republic of China. jgchen@mail.eye.ac.cn.
Jie-Guang
JG
Chen
D000071479:APOBEC-1 Deaminase / Q000096:biosynthesis*; D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000633:toxicity*
D004815:Epidermal Growth Factor; D016202:N-Methylaspartate; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse
Apobec1; Dedifferentiation; Müller glial cells; Nestin; Proliferation