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Development and epigenetic plasticity of murine Müller glia.

Galina Dvoriantchikova | Rajeev J Seemungal | Dmitry Ivanov
Biochimica et biophysica acta. Molecular cell research | 2019

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.

Pubmed ID: 31276697

Associated grants

  • Agency: NEI NIH HHS, United States
    Id: P30 EY014801
  • Agency: NEI NIH HHS, United States
    Id: R01 EY027311

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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Alizadehlab: MeeboChip and HeeboChip Open Source Project (tool)

RRID:SCR_008384

This is an open-source Mouse Exonic Evidence-Based Oligonucleotide Chip (MEEBOChip), and are in the process of building the human counterpart, HEEBOChip. The set of 70mers for MEEBOChip is already available from Illumina, Inc., with synthesis of HEEBOChip 70mers in progress. Both arrays are based on a novel selection of exonic long-oligonucleotides (70-mers) from a genomic annotation of the corresponding complete genome sequences, using a transcriptome-based annotation of exon structure for each genomic locus. Using a combination of existing and custom-tailored tools and datasets (including millions of mRNA and EST sequences), we built and performed a systematic examination of transcript-supported exon structure for each genomic locus at the base-pair level (i.e., exonic evidence). This strategy allowed them to select both constitutive and in many cases alternative exons for nearly every gene in the corresponding genome (e.g., protocadherin locus), allowing an unprecedented exploration of human and mouse biology. Furthermore, they used experimentally derived data to hone the selection of these 70mers, helping maximize their performance under typical fluorescent labeling and hybridization conditions. Specifically, they applied and refined the ArrayOligoSelector algorithm from Joe DeRisis laboratory to select 70mers, considering not only their uniqueness (i.e., hybridization specificity) within the content of the entire genome, but also to overcome the known biases of labeling and hybridization methods (e.g., 3-biased reverse transcription and in vitro transcription reactions).

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SICER (tool)

RRID:SCR_010843

A clustering software package for identification of enriched domains from histone modification ChIP-Seq data.

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Trim Galore (tool)

RRID:SCR_011847

Software tool to automate quality and adapter trimming as well as quality control, with some added functionality to remove biased methylation positions for RRBS sequence files for directional, non-directional or paired-end sequencing. Wrapper around Cutadapt and FastQC to consistently apply adapter and quality trimming to FastQ files, with extra functionality for Reduced Representation Bisulfite Sequencing data.

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TreeView (tool)

RRID:SCR_013503

Software to graphically browse results of clustering and other analyses from Cluster.

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FastQC (tool)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

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Diagenode (tool)

RRID:SCR_014807

Commercial provider of equipment and resources for epigenetics research, biological sample preparation, and diagnostic assays. The products Diagenode provides include automation and semi-automation software, antibodies, reagents, kits, and shearing technologies.

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ChromHMM (tool)

RRID:SCR_018141

Software tool for chromatin state discovery and characterization. Used for chromatin state discovery and genome annotation of non coding genome using epigenomic information across one or multiple cell types. Combines multiple genome wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer complete annotation for each cell type. Provides automated enrichment analysis of resulting annotations.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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