Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse
Abstract Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify Müller glia-specific molecular signatures during retinal development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purifie...
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doaj-d13c75c763564fd2aede7e1fc76eaccc2020-12-08T03:05:09ZengNature Publishing GroupScientific Reports2045-23222017-06-017111210.1038/s41598-017-03874-8Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouseKazuko Ueno0Toshiro Iwagawa1Genki Ochiai2Hideto Koso3Hiromitsu Nakauchi4Masao Nagasaki5Yutaka Suzuki6Sumiko Watanabe7Division of Molecular and Developmental Biology, Institute of Medical Science, University of TokyoDivision of Molecular and Developmental Biology, Institute of Medical Science, University of TokyoDivision of Molecular and Developmental Biology, Institute of Medical Science, University of TokyoDivision of Molecular and Developmental Biology, Institute of Medical Science, University of TokyoDivision of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of TokyoDivision of Biomedical Information Analysis, Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku UniversityDepartment of Medical Genome Sciences, Graduate School of Frontier Sciences, University of TokyoDivision of Molecular and Developmental Biology, Institute of Medical Science, University of TokyoAbstract Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify Müller glia-specific molecular signatures during retinal development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive Müller glia and other EGFP-negative retinal cells from developing retinas and subjected them to RNA sequencing analysis. Gene expression pattern of EGFP-positive cell was similar to genes expressed in retinal progenitors, and they were downregulated in other cell lineages. Then, we examined the modification profiles of H3K27me3 and H3K4me3 by referring to chromatin immunoprecipitation-sequencing data of rods and other cells. Clustering of the H3K4me3 and H3K27me3 values followed by ontology analysis revealed a high incidence of transcription factors including Hes1 in clusters with high H3K27me3 levels. Hes1 expression level decreased dramatically, and the H3K27me3 level at the Hes1-locus was upregulated strongly during retinal development. Furthermore, the Hes1 expression level was upregulated in an Ezh2-knockout retina. These results suggest that downregulation of Müller glia-related genes in other lineage rather than upregulation of them in Müller glia contributed Müller-specific molecular features, and a role for modified H3K27me3 in suppressing Müller glia-related genes in other retinal cell lineages to avoid unfavorable expression.https://doi.org/10.1038/s41598-017-03874-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kazuko Ueno Toshiro Iwagawa Genki Ochiai Hideto Koso Hiromitsu Nakauchi Masao Nagasaki Yutaka Suzuki Sumiko Watanabe |
spellingShingle |
Kazuko Ueno Toshiro Iwagawa Genki Ochiai Hideto Koso Hiromitsu Nakauchi Masao Nagasaki Yutaka Suzuki Sumiko Watanabe Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse Scientific Reports |
author_facet |
Kazuko Ueno Toshiro Iwagawa Genki Ochiai Hideto Koso Hiromitsu Nakauchi Masao Nagasaki Yutaka Suzuki Sumiko Watanabe |
author_sort |
Kazuko Ueno |
title |
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse |
title_short |
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse |
title_full |
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse |
title_fullStr |
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse |
title_full_unstemmed |
Analysis of Müller glia specific genes and their histone modification using Hes1-promoter driven EGFP expressing mouse |
title_sort |
analysis of müller glia specific genes and their histone modification using hes1-promoter driven egfp expressing mouse |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-06-01 |
description |
Abstract Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify Müller glia-specific molecular signatures during retinal development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive Müller glia and other EGFP-negative retinal cells from developing retinas and subjected them to RNA sequencing analysis. Gene expression pattern of EGFP-positive cell was similar to genes expressed in retinal progenitors, and they were downregulated in other cell lineages. Then, we examined the modification profiles of H3K27me3 and H3K4me3 by referring to chromatin immunoprecipitation-sequencing data of rods and other cells. Clustering of the H3K4me3 and H3K27me3 values followed by ontology analysis revealed a high incidence of transcription factors including Hes1 in clusters with high H3K27me3 levels. Hes1 expression level decreased dramatically, and the H3K27me3 level at the Hes1-locus was upregulated strongly during retinal development. Furthermore, the Hes1 expression level was upregulated in an Ezh2-knockout retina. These results suggest that downregulation of Müller glia-related genes in other lineage rather than upregulation of them in Müller glia contributed Müller-specific molecular features, and a role for modified H3K27me3 in suppressing Müller glia-related genes in other retinal cell lineages to avoid unfavorable expression. |
url |
https://doi.org/10.1038/s41598-017-03874-8 |
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