Related Experiment Video
Updated: Mar 8, 2026
Derivation of Glial Restricted Precursors from E13 mice
Published on: June 20, 2012
Apobec1 Promotes Neurotoxicity-Induced Dedifferentiation of Müller Glial Cells
Jian Xiao1, Xue Li1, Lan Chen1
1School 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.
Abstract:
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.
Insights
Neurotoxic treatment triggers retinal Müller cells to proliferate and dedifferentiate. This involves Apolipoprotein B mRNA editing catalytic subunit 1 (Apobec1) upregulating Nestin expression via DNA demethylation, promoting cell cycle reentry.
Area of Science:
- Neuroscience
- Cell Biology
- Ophthalmology
Background:
- Mammalian retinal Müller glial cells exhibit stem/progenitor properties post-neurotoxic insult.
- Molecular mechanisms of adult Müller cell dedifferentiation and proliferation remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms driving Müller cell dedifferentiation and proliferation in the mammalian retina following neurotoxic treatment.
Main Methods:
- Treatment of retinas with N-methyl-D-aspartate (NMDA) and epidermal growth factor (EGF).
- Analysis of Müller cell proliferation and stem cell marker expression (Nanog, Nestin).
- Assessment of DNA methylation patterns in Nanog promoter and Nestin enhancer.
- Overexpression of Apolipoprotein B mRNA editing catalytic subunit 1 (Apobec1) in primary Müller cells.
Main Results:
- NMDA + EGF treatment induced Müller cell proliferation and expression of Nanog and Nestin.
- Increased Nanog and Nestin mRNA correlated with reduced methylation of their respective regulatory regions.
- Apobec1 was upregulated early after NMDA + EGF treatment.
- Apobec1 overexpression in Müller cells increased Nestin expression and decreased Nestin enhancer methylation.
Conclusions:
- Neurotoxicity-induced Apobec1 may promote Müller cell dedifferentiation and cell cycle reentry.
- DNA demethylation of the Nestin enhancer is a potential mechanism mediated by Apobec1.
- This study offers novel insights into Müller cell plasticity in the mammalian retina.
