Myelin regulatory factor (MYRF) is a critical early regulator of retinal pigment epithelial development.

IF 4 2区生物学 Q1 GENETICS & HEREDITY

PLoS Genetics Pub Date : 2025-04-15 eCollection Date: 2025-04-01 DOI:10.1371/journal.pgen.1011670

Michelle L Brinkmeier, Su Qing Wang, Hannah A Pittman, Leonard Y Cheung, Lev Prasov

{"title":"Myelin regulatory factor (MYRF) is a critical early regulator of retinal pigment epithelial development.","authors":"Michelle L Brinkmeier, Su Qing Wang, Hannah A Pittman, Leonard Y Cheung, Lev Prasov","doi":"10.1371/journal.pgen.1011670","DOIUrl":null,"url":null,"abstract":"<p><p>Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in MYRF are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice (Rx > Cre Myrffl/fl) at 3 developmental timepoints. Myrf was expressed specifically in the RPE, and expression was abrogated in Rx > Cre Myrffl/fl eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including Ermn and Upk3b, along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed Myrf downstream or parallel to Pax6 and Mitf and upstream of Sox10 in RPE differentiation. Together, these results suggest a strong role for MYRF in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of Sox10.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 4","pages":"e1011670"},"PeriodicalIF":4.0000,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052213/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pgen.1011670","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in MYRF are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice (Rx > Cre Myrffl/fl) at 3 developmental timepoints. Myrf was expressed specifically in the RPE, and expression was abrogated in Rx > Cre Myrffl/fl eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including Ermn and Upk3b, along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed Myrf downstream or parallel to Pax6 and Mitf and upstream of Sox10 in RPE differentiation. Together, these results suggest a strong role for MYRF in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of Sox10.

查看原文本刊更多论文

髓磷脂调控因子（MYRF）是视网膜色素上皮发育的重要早期调控因子。

髓磷脂调节因子（Myrf）是早期视网膜和视网膜色素上皮发育的关键转录因子，Myrf的人类变异是纳米眼的一个原因。在3个发育时间点对Myrf条件敲除小鼠（Rx > Cre Myrffl/fl）进行单细胞RNA测序（scRNAseq）。Myrf在RPE中特异表达，在Rx > Cre Myrffl/fl眼中不表达。scRNAseq分析显示，在细胞死亡的所有时间点上，RPE细胞的损失都是由细胞死亡引起的。RPE的GO-term分析显示黑色素形成和解剖结构形态发生途径下调，电镜和组织学分析支持这一观点。新的结构靶基因包括Ermn和Upk3b，以及黄斑变性和遗传性视网膜疾病基因被下调，TGFß/BMP信号和效应物被强烈上调。规律分析表明，在RPE分化中，Myrf位于Pax6和Mitf的下游或平行位置，而位于Sox10的上游。综上所述，这些结果表明MYRF通过调节黑色素形成、细胞存活和细胞结构，部分通过抑制TGFß信号传导和激活Sox10，在RPE成熟中发挥重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

PLoS Genetics GENETICS & HEREDITY-

自引率

2.20%

发文量

438

期刊介绍： PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.