July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Development and epigenetic plasticity of murine Müller glia
Author Affiliations & Notes
  • Dmitry V Ivanov
    Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States
    Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Rajeev Seemungal
    Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Galina Dvoriantchikova
    Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Dmitry Ivanov, None; Rajeev Seemungal, None; Galina Dvoriantchikova, None
  • Footnotes
    Support  R01 EY027311; P30EY014801; Research to Prevent Blindness Unrestricted Grant
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3430. doi:
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      Dmitry V Ivanov, Rajeev Seemungal, Galina Dvoriantchikova; Development and epigenetic plasticity of murine Müller glia. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3430.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : An ideal reparative strategy for the retina would be for it to heal itself. The ability to regenerate the entire retina and restore lost sight after injury is found in some species and mostly relies on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progenitors for retinal regeneration, we need to look into Müller glia origins. Here we investigated changes in gene expression during differentiation from retinal progenitor cells (RPCs) in Müller glia. We analyzed the global epigenetic profile of adult Müller glia to understand the epigenetic plasticity of this cell type to be reprogrammed and differentiate into retinal neurons.

Methods : To this end, we isolated Notch1+ (RPCs) and Glast+ (Müller glia) cells from developing murine retinas using an immunomagnetic cell separation approach. The RNA isolated from the samples was used for microarray analysis. To study the global epigenetic profile of adult Müller glia, we used ChIP-seq analysis and whole-genome bisulfite sequencing. Hierarchical and k-means clustering were employed to identify clusters of differentially expressed genes. The epigenetic data was analyzed using Hidden Markov Model and change-point based methods to identify Müller glia chromatin and methylome states in different segments of the genome following genome annotation.

Results : We found that significant changes in gene expression during differentiation of RPCs in Müller glia affect just a small group of genes. We observed a high similarity of Müller glia chromatin and methylome states to progenitors as well as the epigenetic ability of Müller glia to proliferate. Our findings indicate that Müller glia are epigenetically very close to late-born retinal neurons, but not early born retinal neurons. Importantly, key genes, required for cone and rod phototransduction, were highly methylated.

Conclusions : Our data suggest that Müller glia are epigenetically very similar to late RPCs. Meanwhile, obstacles for regeneration of the entire mammalian retina from Müller glia is due to inactive chromatin and methylome states of many genes required for development of early born retinal neurons. However, these inactive chromatin states are most likely temporarily repressed, and may be activated in the presence of some pioneer transcription factors. In addition, demethylase activity may be required for proper reprogramming and differentiation of Müller glia into photoreceptors.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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