ArticleThe Journal of biological chemistry2016
Germ Cell Nuclear Factor (GCNF) Represses Oct4 Expression and Globally Modulates Gene Expression in Human Embryonic Stem (hES) Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells.International journal of molecular sciences · 2023Pooled it
- The nuclear receptor NR6A1 plays an oncogenic role through reprogramming glycolysis in tumors.Biological research · 2025Article
- OAC1 improves mitofusin 2 expression to alleviate neuronal injury following experimental ischemic stroke.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Mitofusin 2 Mediates the Protective Effect of NR6A1 Silencing Against Neuronal Injury in Experimental Stroke Models.Molecular neurobiology · 2025Article
- The expanding roles of Nr6a1 in development and evolution.Frontiers in cell and developmental biology · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Endometrial stem/progenitor cells: Properties, origins, and functions.Genes & diseases · 2023Review
- Article
- Hormone receptor 4 is required in muscles and distinct ovarian cell types to regulate specific steps ofDevelopment (Cambridge, England) · 2021Article
- Marked TGF-β-regulated miRNA expression changes in both COPD and control lung fibroblasts.Scientific reports · 2019Article
- A Novel 13 bp Deletion within theAnimals : an open access journal from MDPI · 2019Article
- NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.Cell communication and signaling : CCS · 2019Article
- Targeted sequencing revealsInternational journal of clinical and experimental pathology · 2019Article
- Nuclear receptors in neural stem/progenitor cell homeostasis.Cellular and molecular life sciences : CMLS · 2017Review
- Site-specific regulation of histone H1 phosphorylation in pluripotent cell differentiation.Epigenetics & chromatin · 2017Article
- A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).Journal of molecular biology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Oct4 is considered a key transcription factor for pluripotent stem cell self-renewal. It binds to specific regions within target genes to regulate their expression and is downregulated upon induction of differentiation of pluripotent stem cells; however, the mechanisms that regulate the levels of human Oct4 expression remain poorly understood. Here we show that expression of human Oct4 is directly repressed by germ cell nuclear factor (GCNF), an orphan nuclear receptor, in hES cells. Knockdown of GCNF by siRNA resulted in maintenance of Oct4 expression during RA-induced hES cell differentiation. While overexpression of GCNF promoted repression of Oct4 expression in both undifferentiated and differentiated hES cells. The level of Oct4 repression was dependent on the level of GCNF expression in a dose-dependent manner. mRNA microarray analysis demonstrated that overexpression of GCNF globally regulates gene expression in undifferentiated and differentiated hES cells. Within the group of altered genes, GCNF down-regulated 36% of the genes, and up-regulated 64% in undifferentiated hES cells. In addition, GCNF also showed a regulatory gene pattern that is different from RA treatment during hES cell differentiation. These findings increase our understanding of the mechanisms that maintain hES cell pluripotency and regulate gene expression during the differentiation process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.