Transcriptome and DNA Methylome Signatures Associated With Retinal Müller Glia Development, Injury Response, and Aging.
Transcriptome and DNA Methylome Signatures Associated With Retinal Müller Glia Development, Injury Response, and Aging.
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DOI：
10.1167/iovs.19-27361
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发表时间：
2019-10
影响因子：
4.4
通讯作者：
Siyuan Lin;Jingyi Guo;Shuyi Chen
中科院分区：
文献类型：
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作者：
Siyuan Lin;Jingyi Guo;Shuyi Chen
目的本研究的目的是系统地表征和关联小鼠Müller细胞的转录组和DNA甲基化组特征，这可能是这些细胞的发育、生理功能和再生能力的基础。方法从表达Müller细胞特异性绿色荧光蛋白（GFP）的小鼠中分离正常、损伤和衰老状态下的Müller细胞。使用RNA测序对转录组进行测序，并使用还原代表性亚硫酸氢盐测序对DNA甲基化组进行测序。使用各种生物信息学工具来比较和关联转录组和DNA甲基化组。结果Müller细胞表达一种独特的转录组，这与其视网膜支持作用和休眠视网膜生成状态一致。损伤显著改变了Müller细胞的转录组，但未能刺激细胞周期机制和视网膜生成因子达到早期视网膜祖细胞（RPC）中观察到的状态。与早期RPC相比，Müller细胞的基因组甲基化程度较低，但Müller细胞和RPC特异性基因的大多数调控元件在Müller细胞和RPC中均类似地低甲基化，除了Müller细胞特异性功能基因的子集。衰老只会微妙地影响穆勒细胞的转录组和DNA甲基化组。结论Müller细胞不能重新激活细胞周期机制和视黄原细胞因子，可能是Müller细胞进入RPC样再生状态的关键障碍。DNA甲基化可能在发育过程中调节Müller细胞特异性功能基因的表达，但可能不参与限制Müller细胞的再生活性。
Purpose The purpose of this study was to systematically characterize and correlate the transcriptome and DNA methylome signatures of mouse Müller cells that may underlie the development, physiological functions, and regeneration capacity of these cells. Methods Mouse Müller cells under normal, injury, and aging conditions were sorted from Müller cell-specific green fluorescent protein (GFP)-expressing mice. RNA sequencing was used to sequence transcriptomes, and reduced representation bisulfite sequencing was used to sequence DNA methylomes. Various bioinformatics tools were used to compare and correlate the transcriptomes and DNA methylomes. Results Müller cells express a distinct transcriptome that is in line with their retinal supporting roles and dormant retinogenic status. Injury changes the Müller cell transcriptome dramatically but fails to stimulate the cell cycle machinery and retinogenic factors to the states observed in early retinal progenitor cells (RPCs). Müller cells exhibit a less methylated genome than that of early RPCs, but most regulatory elements for Müller cell- and RPC-specific genes are similarly hypomethylated in both Müller cells and RPCs, except for a subset of Müller cell-specific functional genes. Aging only subtly affects the transcriptome and DNA methylome of Müller cells. Conclusions Failure to reactivate the cell cycle machinery and retinogenic factors to necessary levels might be key barriers blocking Müller cells from entering an RPC-like regeneration state. DNA methylation might regulate the expression of a subset of Müller cell-specific functional genes during development but is likely not involved in restricting the regeneration activity of Müller cells.