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Biochim Biophys Acta Mol Cell Res. 2019 Oct;1866(10):1584-1594. doi: 10.1016/j.bbamcr.2019.06.019. Epub 2019 Jul 2.

Development and epigenetic plasticity of murine Müller glia.

Author information

1
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: gdvoriantchikova@med.miami.edu.
2
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: rjs313@med.miami.edu.
3
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: divanov@med.miami.edu.

Abstract

The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expression during differentiation of retinal progenitor cells (RPCs) into Müller glia and analyzed the global epigenetic profile of adult Müller glia. We observed significant changes in gene expression during differentiation of RPCs into Müller glia in only a small group of genes and found a high similarity between RPCs and Müller glia on the transcriptomic and epigenomic levels. Our findings also indicate that Müller glia are epigenetically very close to late-born retinal neurons, but not early-born retinal neurons. Importantly, we found that key genes required for phototransduction were highly methylated. Thus, our data suggest that Müller glia are epigenetically very similar to late RPCs; however, obstacles for regeneration of the entire mammalian retina from Müller glia may consist of repressive chromatin and highly methylated DNA in the promoter regions of many genes required for the development of early-born retinal neurons. In addition, DNA demethylation may be required for proper reprogramming and differentiation of Müller glia into rod photoreceptors.

KEYWORDS:

DNA methylation; Development; Epigenetics; Histone modifications; Müller glia; Retina

PMID:
31276697
PMCID:
PMC6684404
[Available on 2019-10-01]
DOI:
10.1016/j.bbamcr.2019.06.019
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