Similar Datasets
Project description:Transcriptional changes associated with Myrf deletion in mouse ES cells.
| PRJNA1013107 | ENA
Project description:We have created a Myrf knockdown (Myrf +/−) mutant mouse strain and investigated the molecular phenotype of reduced MYRF expression in the retina using RNA-sequencing. As an initial finding, photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology were found in Myrf +/− mice, indicating an important role of MYRF in retinal development.It was revealed through RNA-seq that the expression of phototransduction and estrogen signaling pathways reduced in Myrf +/− mice. Thus, alterations of phototransduction and estrogen signaling pathways seem to play important roles in connecting Myrf deficiency with retinal photoreceptor defects.
2020-09-12 | GSE157806 | GEO
Project description:Our research revealed that the transmembrane transcription factors MYRF-1 and MYRF-2 are crucial for activating the microRNA lin-4 at the end of the first larval stage in C. elegans. To determine whether MYRF regulates other microRNA genes during this period, we conducted a microRNA sequencing analysis to compare microRNA expression in late L1 larvae of wild type and myrf-1(ju1121) mutants. The myrf-1(ju1121) mutation causes a loss of function in both MYRF-1 and MYRF-2. Our analysis identified a subset of microRNAs that were differentially expressed between the wild type and the myrf-1(ju1121) mutants.
2024-03-31 | GSE262766 | GEO
Project description:Improper light focus on the retina, refractive error, is primarily caused by eye size differences and is the leading cause of vision loss worldwide. C-terminal variants in the Myelin Regulatory Factor (MYRF) gene, a retinal pigment epithelium (RPE)-derived transcription factor, lead to isolated nanophthalmos characterized by a small, though structurally sound eye. However, other MYRF loss-of-function variants cause syndromic disease. To address this discrepancy, in vitro and animal studies were performed on a pathogenic C-terminal variant dG-MYRF (p.Gly1126fs30*, c.3376-1G>A ). Human RPE-cells or primary RPE transduced with dG-MYRF showed reduced target gene expression, with decreased steady-state levels of the C-terminal cleavage product, but normal cleavage and localization. A homozygous humanized MYRF C-terminal mouse model (MyrfhumdG/humdG) was embryonic lethal by embryonic day (E) 18.5, while wildtype (MyrfhumWT/humWT) mice were viable. Single-cell RNA-seq from E17.5 MyrfhumdG/humdG and knockout RxCre;Myrffl/fl (E15.5 and P0) mice revealed shared differentially expressed genes, with decreased effect size in the MyrfhumdG/humdG eyes. These findings support dG-MYRF as a hypomorphic allele. Additionally, two novel MYRF splicing variants creating nonfunctional isoforms were found in families with isolated nanophthalmos. Overall, hypomorphic MYRF alleles underlie isolated nanophthalmos, supporting a tissue-specific threshold effect and highlighting unique roles for the MYRF C-terminus in the RPE.
2025-12-01 | GSE310659 | GEO
Project description:Embryonic stem (ES) cells and embryos reversibly pause via chemical mTOR inhibition. In this study, we investigate the tissue-specific response to mTORi-induced pausing in ES and trophoblast stem (TS) cells. To resolve the sequential rewiring of the proteome, we conducted a time-series proteomics experiment at 1, 3, 6, 12, 24, and 48 hours upon induction of pausing, and at 1, 3, 6, 12, 24, and 48 hours upon release of pausing in ES and TS cells. We find that ES, but not TS cells pause reversibly. To optimise developmental pausing conditions, we reasoned that by understanding the difference in pausing response of ES and TS cells, we could identify which pathways are essential for pausing. We found that KEGG pathways related to amino acid degradation, fatty acid degradation, and DNA repair are upregulated in ES cells, but downregulated in TS cells during entry into pausing. Moreover, by targeted metabolomics, we found a depletion of short chain carnitines in the paused ES cells. To extend the length of developmental pausing, we supplemented paused embryos with L-carnitine. The L-carnitine supplementation facilitates lipid usage and prolongs the pausing length by 19 days through the establishment of a more dormant state.
2023-11-06 | PXD033750 | Pride
Project description: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 of 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.
2025-01-01 | GSE269598 | GEO
Project description: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 of 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.
2025-01-01 | GSE269597 | GEO
Project description: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 of 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.
2025-01-01 | GSE269599 | GEO
Project description:Many tumors of endodermal origin are composed of highly secretory cancer cells that must adapt endoplasmic reticulum (ER) activity to enable proper folding of secretory proteins, prevent ER stress and thus maintain their viability. In pancreatic ductal adenocarcinoma (PDAC), well-differentiated and secretory cancer cells coexist with poorly differentiated cells with quasi-mesenchymal features. We found that the differentiated PDAC cells, but not the undifferentiated ones, expressed an ER membrane-associated transcription factor (TF), Myelin Regulatory Factor (MYRF), that is released by self-cleavage and translocates to the nucleus. MYRF expression was directly controlled by HNF1B, a TF maintaining epithelial identity in PDAC, and it acted to fine-tune the expression of genes encoding highly glycosylated and cysteine-rich secretory proteins, thus preventing ER overload. MYRF-deficient PDAC cells showed anatomical and biochemical signs of ER stress, impaired proliferation and inability to form spheroids in vitro, while in vivo they generated highly secretory but poorly proliferating and hypo-cellular tumors. These data indicate a role of MYRF in the control of homeostasis and proliferation of cancer cells with high secretory activity
2020-09-18 | GSE145628 | GEO
Project description:Many tumors of endodermal origin are composed of highly secretory cancer cells that must adapt endoplasmic reticulum (ER) activity to enable proper folding of secretory proteins, prevent ER stress and thus maintain their viability. In pancreatic ductal adenocarcinoma (PDAC), well-differentiated and secretory cancer cells coexist with poorly differentiated cells with quasi-mesenchymal features. We found that the differentiated PDAC cells, but not the undifferentiated ones, expressed an ER membrane-associated transcription factor (TF), Myelin Regulatory Factor (MYRF), that is released by self-cleavage and translocates to the nucleus. MYRF expression was directly controlled by HNF1B, a TF maintaining epithelial identity in PDAC, and it acted to fine-tune the expression of genes encoding highly glycosylated and cysteine-rich secretory proteins, thus preventing ER overload. MYRF-deficient PDAC cells showed anatomical and biochemical signs of ER stress, impaired proliferation and inability to form spheroids in vitro, while in vivo they generated highly secretory but poorly proliferating and hypo-cellular tumors. These data indicate a role of MYRF in the control of homeostasis and proliferation of cancer cells with high secretory activity
2020-09-18 | GSE145627 | GEO